concanavalin-a and Chronic-Disease

Peripheral T cells from patients with chronic active hepatitis (CAH) showed a significantly decreased suppressor effect (or increased helper effect) on allogeneic B cell differentiation into Ig-producing cells (Ig-PC) (p less than 0.05). After irradiation of T cells to eliminate suppressor influences, mean spontaneous helper activity of CAH was not different from that of healthy subjects, indicating that spontaneous helper activity of CAH was normal. Concanavalin A (Con A)-induced suppressor cell activity was significantly decreased in CAH (p less than 0.01, 9 defective cases out of 18 patients). Minor defect of Con A-induced suppressor activity was also found in some patients with chronic persistent hepatitis (CPH) (2 defective cases out of 14 patients). Autologous mixed lymphocyte reaction (AMLR) was significantly decreased in patients with CAH (p less than 0.005). Spontaneous suppressor or Con A-induced suppressor activity was not different statistically between HBsAg-positive and HBsAg-negative cases. Finally, we demonstrated a presence of a serum factor(s) that can decrease Con A-induced suppressor cell function of healthy subjects in 7 of 21 patients with CAH and 2 of 14 CPH. Our results suggest that defective suppressor cell function likely attributable to serum factor(s) may reflect altered immune responses of CAH.

Topics: B-Lymphocytes; Cell Differentiation; Chronic Disease; Concanavalin A; Female; Hepatitis; Humans; In Vitro Techniques; Lymphocyte Culture Test, Mixed; Male; T-Lymphocytes; T-Lymphocytes, Regulatory

We have recently demonstrated that ConA-induced suppressor cell function is defective in chronic inflammatory demyelinating polyneuropathy (CIDP). To assess whether this defect plays a role in disease activity and its reversal is important in recovery, we studied modifications of ConA-induced suppressor cell function induced by prednisone and plasma exchange in 20 patients with CIDP. We found a significant increase towards normal of ConA-induced suppressor cell function after treatment in concurrence with clinical improvement. Induction of suppression, presumably through favorable modifications of the cytokine network or other humoral mediators, might be one, among others, of the mechanisms through which prednisone and plasma exchange are effective in CIDP.

Topics: Adolescent; Adult; Aged; Anti-Inflammatory Agents; Child; Chronic Disease; Combined Modality Therapy; Concanavalin A; Cytokines; Demyelinating Diseases; Female; Humans; Immunosuppression Therapy; Leukocytes; Male; Middle Aged; Plasma Exchange; Polyradiculoneuropathy; Prednisone

Concanavalin A (Con A) affinity electrophoresis of serum alpha-fetoprotein (AFP) can distinguish hepatocellular carcinoma (HCC) from other malignancies when the serum AFP concentration is elevated. However, Con A has not been able to distinguish HCC from benign chronic liver disease such as cirrhosis or chronic hepatitis.. The Con A affinity electrophoresis of serum AFP was analyzed in patients with a serum AFP concentration greater than 50 ng/mL by antibody affinity electrophoresis and Western blotting in an attempt to distinguish hepatocellular carcinoma from benign chronic liver disease. Before the assay, the serum AFP concentrations were adjusted between 100 ng/ml and 300 ng/ml by concentrating or diluting the samples.. Of 180 patients with HCC, 44 (24%) had a single band and 91 (51%), 35 (19%), and 10 (6%) had 2, 3, and 4 bands, respectively. All 35 patients with chronic hepatitis had a single band. All but 1 of 72 patients with cirrhosis had a single band. Multiple AFP bands on Con A affinity electrophoresis appear to be diagnostic of HCC. This method has a sensitivity of 76%, a specificity of 99%, a positive predictive value of 99%, and a negative predictive value of 71% for detecting HCC. The number of AFP bands correlated with serum AFP concentration and tumor size in patients with HCC.. This assay is useful for distinguishing HCC from benign chronic liver diseases.

Topics: Adult; Aged; alpha-Fetoproteins; Blotting, Western; Carcinoma, Hepatocellular; Chi-Square Distribution; Chronic Disease; Concanavalin A; Diagnosis, Differential; Electrophoresis; Female; Hepatitis; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity

A double-blind, randomized, crossover chronic study was done to determine the efficacy of colchicine in 10 atopic patients with asthma. A constant dose of sustained-release theophylline and albuterol by inhalation, as needed, was administered. Compared to placebo, colchicine, 0.5 mg twice daily, significantly reduced the mean (+/- SEM) daily clinical score from 2.18 +/- 0.34 to 1.64 +/- 0.32 (p less than 0.05), and the daily number of inhalations of albuterol from 5.89 +/- 1.48 to 4.01 +/- 1.26 (p less than 0.02). Colchicine significantly (p less than 0.05) increased the concanavalin A-induced suppressor cell function from 16.2 +/- 4.6% to 39.0 +/- 10.7%, which was similar to healthy volunteers (41.1 +/- 3.5%). Furthermore, colchicine significantly (p less than 0.05) decreased serum IgE from 248 +/- 63 to 188 +/- 46 IU/ml. Colchicine had no significant effect on pulmonary function tests, the early phase reaction of antigen-induced bronchial inhalation challenge, and immediate skin test responses. Thus, colchicine has immunomodulatory effects that may perhaps have a mild benefit in the treatment of asthma.

Topics: Adolescent; Adult; Albuterol; Asthma; Bronchial Provocation Tests; Chronic Disease; Colchicine; Concanavalin A; Delayed-Action Preparations; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lung; Male; Randomized Controlled Trials as Topic; Skin Tests; T-Lymphocytes, Regulatory; Theophylline

Dry eye disease (DED) currently has no satisfactory treatment partly because of the lack of informative animal models. We evaluated the anti-inflammatory phosphosulindac (PS) for the treatment of DED using a new rabbit model of DED based on the concanavalin A (Con A) acute DED model: we injected all lacrimal glands with Con A weekly under ultrasound guidance, which prolonged DED to >3 weeks, and thoroughly assessed efficacy with tear break-up time (TBUT), tear osmolarity, Schirmer test, and tear lactoferrin levels. Rabbits with DED (n = 8-10 eyes per group) were treated topically with PS or vehicle 3×/day for 21days. PS restored TBUT, tear osmolarity, and lactoferrin levels (P < 0.0001-0.04) to normal but did not significantly improve the results of the Schirmer test. PS showed no side effects and was much more efficacious than cyclosporine or lifitegrast. In the cornea, PS suppressed the activation of nuclear factor kappa-B, the levels of transforming growth factor beta, interleukin-1 beta, interleukin-6, and interleukin-8, and the levels of matrix metalloproteinase (MMP)-1 and MMP-9, and MMP activity. Levels of prostaglandin E

Topics: Administration, Ophthalmic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Chronic Disease; Concanavalin A; Cytokines; Dinoprostone; Disease Models, Animal; Dry Eye Syndromes; Humans; Lactoferrin; Matrix Metalloproteinase 1; Matrix Metalloproteinase 9; Organophosphorus Compounds; Osmolar Concentration; Rabbits; Sulindac; Tears

Liver resident macrophages designated Kupffer cells (KCs) form the largest subpopulation of tissue macrophages. KCs are involved in the pathogenesis of liver inflammation. However, the role of KCs in the systemic inflammation is still elusive. In this study, we examined whether KCs are involved in not only intrahepatic inflammation but also extrahepatic systemic inflammation. Administration of clodronate liposomes resulted in the KC deletion and in the suppression of liver injury in T cell-mediated hepatitis by ConA as a local acute inflammation model, while the treatment did not influence dextran sulfate sodium- (DSS-) induced colitis featured by weight loss, intestinal shrink, and pathological observation as an ectopic local acute inflammation model. In contrast, KC deletion inhibited collagen-induced arthritis as a model of extrahepatic, systemic chronical inflammation. KC deleted mice showed weaker arthritic scores, less joint swelling, and more joint space compared to arthritis-induced control mice. These results strongly suggest that KCs are involved in not only intrahepatic inflammatory response but also systemic (especially) chronic inflammation.

Topics: Acute Disease; Animals; Arthritis, Experimental; Chronic Disease; Colitis; Collagen; Concanavalin A; Dextran Sulfate; Disease Models, Animal; Female; Inflammation; Kupffer Cells; Liver; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Inbred ICR

Arginine deficiency and chronic inflammation may cause immune dysfunction. The authors previously showed that a pharmacological dose of parenteral arginine facilitates ornithine rather than nitric oxide production in subacute peritonitis. Herein, they investigated the effects of different doses of parenteral arginine supplementation on immunocytic subpopulation distribution and function.. Male Wistar rats that underwent cecal punctures for induction of subacute peritonitis were infused with conventional parenteral nutrition solution (1.61% of total calories as arginine) or solutions supplemented with low-, medium-, or high-dose arginine (2.85%, 4.08%, and 6.54% of total calories, respectively) for 7 days. Distributions of T cells, B cells, and monocytes/macrophages and cytokine productions of peripheral blood lymphocytes (PBLs) and splenocytes were analyzed.. There were no significant differences in circulating white blood cell numbers and serum tumor necrosis factor (TNF)-α and interferon (IFN)-γ concentrations among groups. Serum nitrate/nitrite (NOx) and interleukin (IL)-2 levels were significantly decreased by arginine in a dose-dependent manner. Animals supplemented with parenteral arginine had significantly decreased productions of concanavalin (Con) A- and lipopolysaccharide (LPS)-stimulated TNF-α in PBLs and splenocytes, spontaneous IL-6 and LPS-stimulated IFN-γ in PBLs, and LPS-stimulated IL-6 in splenocytes. In addition, low-dose arginine significantly increased production of spontaneous IFN-γ in PBLs and splenocytes. High-dose arginine significantly increased spontaneous TNF-α, and Con A stimulated IL-4 and IL-6 in PBLs.. Parenteral arginine administration at approximately 4% of total calories may alter PBLs and splenocytic immunity, and >6% of total calories might not be of benefit in rats with subacute peritonitis.

Topics: Animals; Arginine; Chronic Disease; Concanavalin A; Cytokines; Deficiency Diseases; Dietary Supplements; Dose-Response Relationship, Drug; Immunity; Inflammation; Inflammation Mediators; Leukocytes; Lipopolysaccharides; Macrophages; Male; Nitrates; Nitrites; Parenteral Nutrition; Peritonitis; Rats; Rats, Wistar; Spleen

Melatonin by exhibiting antioxidant, anti-aging, and immunomodulatory properties favorably modulate the immune function, protecting the hosts from several infectious diseases. Zinc is an essential trace element important for the efficiency of the immune system in reason of its widespread role in the activity of enzymes, transcription factors and cytokines. The etiology of Chagas' disease, caused by a protozoan parasite Trypanosoma cruzi, has been the focus of considerable discussion, although chronic phase still remains not fully understood. This study showed that zinc and melatonin treatment did not affect the percentage of both CD4+ and CD8+ T lymphocytes subsets in chronically infected animals. Increased levels of IL-2 and IL-10, as well as, enhanced thymocyte proliferation in T. cruzi infected groups under zinc and melatonin therapy was observed as compared to untreated group. Conversely, during the chronic phase of infection, macrophages counts were reduced in melatonin and zinc-melatonin treated animals. The combined actions of zinc and melatonin have beneficial effects in counteracting parasite-induced immune dysregulation, protecting animals against the harmful actions of chronic T. cruzi infection. Furthermore, our results provide an experimental basis for further studies on the role of immunomodulatory therapies.

Topics: Animals; Antigens, CD; Cell Count; Cell Proliferation; Chagas Disease; Chronic Disease; Concanavalin A; Cytokines; Interleukin-10; Interleukin-2; Macrophages, Peritoneal; Male; Melatonin; Parasitemia; Phenotype; Rats; Rats, Wistar; Thymocytes; Trypanosoma cruzi; Zinc

Feline immunodeficiency virus (FIV) infection is characterized by chronic overactivation of immune and inflammatory system, resulting in anergic state and dysfunction of immune cells. Lactoferrin (LF), a glycoprotein present in exocrine secretions and neutrophils, plays an important role in host defense system. Our previous study showed that oral administration of bovine LF (bLF) suppressed oral inflammation, improved the clinical symptoms and decreased serum gamma-globulin as a marker of inflammation in FIV-infected cats with intractable stomatitis. The anti-inflammatory effect was partly involved in regulation of neutrophil function by bLF. In this study, to clarify the relationship between anti-inflammatory effects of bLF and peripheral blood mononuclear cells (PBMC), we examined the effect of bLF on proliferation, cell cycle progression and cytokine expression in mitogen-activated PBMC. MTT [3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyl tetrazolium bromide] assay showed that bLF inhibited the concanavalin A (ConA)-induced cell proliferation in FIV-infected cats with the asymptomatic carrier and AIDS-related complex (ARC) phase. Bovine LF restored ConA-induced cell cycle progression and resulted in suppression of the induced apoptosis in feline PBMC. Real-time RT-PCR showed that bLF suppressed ConA-induced expression of interferon-gamma and interleukin-2 in cells of the ARC group regardless of the time of its addition to the medium. These results suggest the hypothesis that therapy with bLF may have the potential to improve and protect functions of overactivated lymphocytes by modulating the cell proliferation, cell cycle and cytokines expression in cats in terminal stage of FIV infection.

Topics: Animals; Cat Diseases; Cats; Cattle; Cell Proliferation; Chronic Disease; Concanavalin A; Cytokines; Female; Gene Expression Regulation; Immunodeficiency Virus, Feline; Lactoferrin; Lentivirus Infections; Leukocytes, Mononuclear; Male; RNA, Messenger

The purpose of this study was to determine whether activating the conjunctival macrophages would affect the course of Acanthamoeba spp. keratitis in a Chinese hamster model of this disease. Chinese hamster spleen cells were stimulated with concanavalin A (Con A), and interferon gamma (IFN-gamma) -containing supernatants were collected 24 hr later. The IFN-gamma-containing supernatants were loaded into liposomes, which were fed to peritoneal macrophages in vitro. Macrophage activation was assessed by testing for production of nitric oxide (NO) with the use of Griess reagent. Conjunctival macrophages were activated in situ by subconjunctival injection of liposomes containing Con A-activated spleen cell culture supernatants. Control liposomes were loaded with phosphate-buffered saline (PBS). Macrophages exposed to supernatants from Con A-stimulated spleen cells produced 4-fold-higher amounts of NO than unstimulated macrophages. Activation of macrophages via subconjunctival injection of liposomes containing supernatants from Con A-stimulated spleen cell cultures resulted in rapid resolution of the corneal infection. Approximately 80% of animals treated with PBS-containing liposomes demonstrated evidence of corneal disease at day 14 compared to 10% incidence of infection in the Con A-treated group. Moreover, at all time points examined, the clinical appearance of the keratitis in animals treated with liposomes containing Con A supernatant was significantly reduced compared to the group treated with liposomes containing PBS (P < 0.05). Macrophages stimulated with IFN-gamma-containing supernatants killed significant numbers of the trophozoites in vitro (P < 0.05). Killing was inhibited by cytochalasin D, but not by L-N6-1-iminoethyl-L-lysine dihydrochloride (L-NIL), which is a selective inhibitor of inducible NO synthase (INOS).

Topics: Acanthamoeba castellanii; Acanthamoeba Keratitis; Animals; Cell Line; Cells, Cultured; Chronic Disease; Concanavalin A; Conjunctiva; Cricetinae; Cricetulus; Humans; Incidence; Interferon-gamma; Macrophage Activation; Macrophages, Peritoneal; Phagocytosis; Severity of Illness Index

Disease progression of feline immunodeficiency virus (FIV) infection is characterized by up-regulation of B7.1 and B7.2 costimulatory molecules and their ligand CTLA4 on CD4(+) and CD8(+) T cells. The CD4(+)CTLA4(+)B7(+) phenotype described in FIV(+) cats is reminiscent of CD4(+)CD25(+)CTLA4(+) cells, a phenotype described for immunosuppressive T regulatory (Treg) cells. In the present study, we describe the phenotypic and functional characteristics of CD4(+)CD25(+) T cells in PBMC and lymph nodes (LN) of FIV(+) and control cats. Similar to Treg cells, feline CD4(+)CD25(+) but not CD4(+)CD25(-) T cells directly isolated from LN of FIV(+) cats do not produce IL-2 and fail to proliferate in response to mitogen stimulation. Unstimulated CD4(+)CD25(+) T cells from FIV(+) cats significantly suppress the proliferative response and the IL-2 production of Con A-stimulated autologous CD4(+)CD25(-) T cells compared with unstimulated CD4(+)CD25(+) T cells from FIV(-) cats. Flow-cytometric analysis confirmed the apparent activation phenotype of the CD4(+)CD25(+) cells in LN of chronically FIV(+) cats, because these cells showed significant up-regulation of expression of costimulatory molecules B7.1, B7.2, and CTLA4. These FIV-activated, anergic, immunosuppressive CD25(+)CTLA4(+)B7(+)CD4(+) Treg-like cells may contribute to the progressive loss of T cell immune function that is characteristic of FIV infection.

Topics: Animals; Antigens, CD; Antigens, Differentiation; Antigens, Viral; B7-1 Antigen; B7-2 Antigen; Cats; Cell Division; Cell Separation; Cells, Cultured; Chronic Disease; Coculture Techniques; Concanavalin A; CTLA-4 Antigen; Feline Acquired Immunodeficiency Syndrome; Immune Tolerance; Immunodeficiency Virus, Feline; Immunophenotyping; Interleukin-2; Ligands; Lipopolysaccharides; Lymph Nodes; Lymphocyte Activation; Lymphocyte Count; Membrane Glycoproteins; Receptors, Interleukin-2; T-Lymphocyte Subsets; T-Lymphocytes, Regulatory; Up-Regulation

The production of nitric oxide (NO) by intraperitoneal macrophages of mice during secondary infection with Echinococcus multilocularis mediates immunosuppression at early and late stages of infection. We addressed the role of NO in host resistance against this extracellular metazoan parasite by infecting inducible nitric oxide synthase knockout ((iNOS-KO) mice (of the C57BL/6 background) with 100 metacestode vesicles. The parasite weight was significantly lower in iNOS-KO mice when compared with wild-type (WT) mice at 4 months postinfection (late stage), thus demonstrating that iNOS deficiency confers a certain degree of resistance against persistent chronic infection. However, histological analysis of periparasitic tissue showed no differences between WT and iNOS-KO mice, as both exhibited granuloma formation and the presence of giant cells. Together with histology, the production of a high level of interferon-gamma (IFN-gamma) in infected iNOS-KO mice upon stimulation with concanavalin A (Con A) and VF-antigen indicated normal T-cell signalling in these animals. As expected, peritoneal exudate cells (PEC) from infected iNOS-KO mice produced no detectable NO, while the PEC from infected WT mice produced high levels of NO after stimulation with lipopolysaccharide (LPS) and parasite protein or carbohydrate antigen, or even without in vitro stimulation. Consequently, the high level of NO production observed during chronic infection in WT mice appears to contribute more to immunosuppression than to limitation of parasite growth. This is also reflected by the fact that splenocyte proliferation was significantly higher and parasite masses lower in iNOS-KO mice (at 1 and 4 months postinfection) than in WT mice.

Topics: Animals; Antigens, Helminth; Cell Division; Cells, Cultured; Chronic Disease; Concanavalin A; Echinococcosis; Echinococcus; Female; Immune Tolerance; Immunity, Innate; Interferon-gamma; Liver; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Spleen

There is increasing evidence that stress produces changes in various immune processes. Some of these changes may be due to neurochemical and hormonal alterations including thyroid hormones levels. This work was carried out to study the impact of chronic mild stress (CMS) exposure on proliferative responses and its correlation with serum thyroid hormone levels. In addition, the influence of serum corticosterone levels on these responses was also studied. For this purpose, mice were submitted from1 to 6 weeks to a CMS model. After undergoing the stress schedule for 4 weeks, an alteration in the proliferative response was observed. Lymphocytes from exposed animals showed a decrease in T-cell response to concanavalin-A (Con A) and phytohemagglutinin (PHA) and an increase in B-cell proliferation to lipopolysaccharides (LPS). In parallel, a reduction in T3 and T4 serum levels was observed. On the contrary, serum corticosterone levels increased in animals exposed to CMS for 1 or 2 weeks and then return to normal values. Lowering serum thyroid hormone levels by propylthiouracil (PTU) treatment negatively modulates T-cell response without affecting B-cell response. On the other hand, the substitutive T4 treatment in stressed animals improved significantly the proliferative T-cell response. Non-significative changes in CD4/CD8 ratio were observed neither in stressed, PTU- or T4-treated animals. Taken together, our results suggest an impact of chronic stress on thyroid function that in turn alters T-cell response. These findings may help to elucidate the physiological mechanisms through which stress plays a roll in the etiology of many diseases.

Topics: Animals; Cell Division; Chronic Disease; Concanavalin A; Corticosterone; Disease Models, Animal; Female; Flow Cytometry; Lipopolysaccharides; Lymphocyte Activation; Lymphocytes; Mice; Mice, Inbred BALB C; Mitogens; Stress, Physiological; Thyroid Hormones; Time Factors

Chronic stress is known to induce immunological disorders. In the present study we examined the consequences of chronic restraint stress on the immune response to tetanus toxin in mice. We investigated the repartition of subsets of lymphoid cells in blood and spleen, the functional ability of lymphocytes to proliferate and to produce cytokines, and antibody titres against tetanus toxin following stress. We report discordance of the stimulation index of lymphocytes in the restraint group: the proliferating rate severely decreased following stimulation with a relevant antigen, whereas it increased with mitogen. Thus, we report a decrease in cytokine production with relevant antigen (interferon-gamma and interleukin-10), without a T helper type 1 and 2 secretion imbalance. Moreover, we observed an alteration in the humoral response, including a delay in isotype maturation and an immunoglobulin G1/G2a imbalance.

Topics: Animals; Cell Division; Chronic Disease; Concanavalin A; Corticosterone; Cytokines; Immunoglobulin G; Immunoglobulin M; Lymphocyte Activation; Lymphocyte Subsets; Male; Mice; Mice, Inbred BALB C; Spleen; Stress, Physiological; T-Lymphocyte Subsets; Tetanus Toxin

This cross-sectional study investigated whether active and avoidance coping methods were differentially related to immune function depending on stress level. Perceived stress and coping method were assessed in 173 healthy older adults and related to the number and percentage of CD3+, CD4+, and CD8+ T lymphocytes as well as the proliferative response of peripheral blood leukocytes to phytohemagluttinin (PHA) and concanavalin A (Con A). Both active and avoidance coping significantly interacted with perceived stress on proliferative responses to both mitogens. Higher levels of active coping were significantly related to a more vigorous proliferative response to PHA and Con A, particularly at high stress levels. At low stress levels, active coping was not significantly related to proliferative responses, whereas avoidance coping was significantly associated with a greater proliferative response to Con A. These results suggest that the relationships between certain coping methods and immune function depend on perceived stress level.

Topics: Adaptation, Psychological; Avoidance Learning; Awareness; Caregivers; Chronic Disease; Concanavalin A; Cross-Sectional Studies; Family Health; Follow-Up Studies; Health Status; Humans; Leukocytes; Phytohemagglutinins; Stress, Psychological; T-Lymphocytes

Endothelial activation is an important feature of many inflammatory diseases and has been implicated as the cause of vascular complications in disorders such as diabetes, atherosclerosis, and transplant rejection. One of the most potent activators of the endothelium is TNF, which can also be expressed by endothelial cells, causing a permanent, autocrine stimulatory signal. To establish a model of continuous endothelial activation and to elucidate the role of endothelial derived TNF in vivo, we generated transgenic mice expressing a noncleavable transmembrane form of TNF under the control of the endothelial-specific tie2 promoter. Adult tie2-transmembrane TNF-transgenic mice developed chronic inflammatory pathology in kidney and liver, characterized by perivascular infiltration of mononuclear cells into these organs. Along with the infiltrate, an up-regulation of the adhesion molecules ICAM-1 and VCAM-1, but not E-selectin, in the endothelium was observed. Despite predisposition to chronic inflammation these mice were protected from immune-mediated liver injury in a model of Con A-induced acute hepatitis. Although the blood levels of soluble TNF and IFN-gamma were increased in transgenic animals after challenge with Con A, no damage of hepatocytes could be detected, as assessed by the lack of increase in plasma transaminase activities and the absence of TUNEL staining in the liver. We conclude that expression of transmembrane TNF in the endothelium causes continuous endothelial activation, leading to both proinflammatory and protective events.

Topics: Acute Disease; Animals; Cell Adhesion Molecules; Chemical and Drug Induced Liver Injury; Chronic Disease; Concanavalin A; Endothelium, Vascular; Inflammation; Kidney; Liver; Membrane Proteins; Mice; Mice, Transgenic; Receptor Protein-Tyrosine Kinases; Receptor, TIE-2; RNA, Messenger; Tumor Necrosis Factor-alpha; Up-Regulation

In some parasitic infections immunosuppression is a prominent characteristic of the host-parasite interplay. We have used a murine alveolar echinococcosis (AE) model in susceptible C57BL/6 mice to document a suppressed splenocyte proliferative response to concanavalin A (Con A) at the early (1-month) stage and to Echinococcus multilocularis-crude antigen (Emc-antigen) at the late (4-6-month) stage of chronic infection. Despite proliferative suppression, splenic cytokine production [interleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma)] in response to Con A or Emc-antigen stimulation was not suppressed at 1 month postinfection (p.i.). Infection resulted in a strong Mac-1+ cell infiltration of the peritoneal cavity and spleen. Peritoneal cells (PEC) from mice infected at the 1-month stage were rich in macrophages and expressed significantly higher levels of transcripts for the inflammatory cytokine IL-1beta and for tumour necrosis factor-alpha and inducible nitric oxide synthase (iNOS), when compared with PEC from non-infected control mice. Conversely, the IL-10 transcript level remained low and did not change during infection. Spleen cells supplemented with PEC from infected mice induced a marked increase in the levels of nitrite in response to Con A and Emc-antigen stimulation, and also a complete suppression of splenic proliferation. The spleen cells from late-stage infected mice expressed only background levels of IL-10 but greatly increased levels of iNOS, when compared with normal spleen cells. This observation correlated with the immunosuppression demonstrated at the late stage of murine AE. Furthermore, the suppressed splenic proliferative responses observed at the early and late stage were reversed to a large extent by the addition of NG-monomethyl-l-arginine and partially by anti-IFN-gamma. Thus, our results demonstrated that the immunosuppression observed in chronic AE was not primarily dependent on IL-10 but rather on nitric oxide production by macrophages from infected animals.

Topics: Animals; Antigens, Helminth; Cell Culture Techniques; Cell Division; Chronic Disease; Concanavalin A; Cytokines; Echinococcosis, Pulmonary; Echinococcus; Enzyme Inhibitors; Female; Immune Tolerance; Interferon-gamma; Macrophage-1 Antigen; Mice; Mice, Inbred C57BL; Nitric Oxide; omega-N-Methylarginine; Peritoneal Cavity; Reverse Transcriptase Polymerase Chain Reaction; Spleen

Here we demonstrate that T. cruzi antigen molecule SAPA (shed acute phase antigen) with neuraminidase-trans sialidase activity triggers down-regulation of T lymphocyte proliferation by interacting with T lymphocyte muscarinic acetylcholine receptors (mAChR). SAPA attachment to mAChR from Lyt 2.2+ T cells resulted in synthesis of cyclic GMP (cGMP) and secretion of PGE2, an immunoregulator effector substance. These T suppressor cell signals were blunted by atropine and by indomethacin. Cell sorter analysis showed that the interaction of SAPA with purified T cells, affected the ratio of L3T4+/Lyt 2.2+ T cells increasing the percentage of Lyt 2.2+ T cells, effect that was inhibited by the mAChR antagonist, atropine. The interaction between SAPA and mAChR from Lyt 2.2+ T cells may result, therefore, in the down-regulation of the host immune response as consequence of T suppressor/cytotoxic cells activation and PGE2 release as they were observed. These results support the theory of an immunosuppressive state that contribute to the chronic course of Chagas' disease.

Topics: Animals; Antigens, Protozoan; Atropine; Cell Division; Chagas Disease; Chronic Disease; Concanavalin A; Cyclic GMP; Cyclooxygenase Inhibitors; Dinoprostone; Down-Regulation; Indomethacin; Mice; Mice, Inbred BALB C; Muscarinic Antagonists; Receptors, Muscarinic; T-Lymphocytes; Trypanosoma cruzi

Splenic lymphocytes and peritoneal macrophages from BALB/c mice with Escherichia coli pyelonephritis were obtained at various intervals after infection. These cells were stimulated in vitro with different antigens and cytokine release was assayed in the supernate of the cultured cells. It was observed that both specific antigens such as outer-membrane proteins (OMPs), porins and heat-shock protein-65 (hsp-65), as well as non-specific mitogens such as phytohaemagglutinin (PHA), were able to induce cytokine production by splenic cells from infected mice. Of all these antigens, hsp-65 was found to be the best inducer of cytokine release. In the acute stage of pyelonephritis, the release of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) was found to increase with time; both reached their peak values on the seventh day after infection. The TH1 pattern of cytokine secretion by splenic cells was observed, i.e., IL-2 and IFN-gamma, whereas there was complete absence of IL-4 secretion. In the chronic stage of pyelonephritis, i.e., 150 days after infection, a decrease in the level of IL-2 and IFN-gamma was observed. Peritoneal macrophages released IL-1 on stimulation with hsp-65, which increased with the progression of disease. The possible implications of this study for the disease process are discussed.

Topics: Acute Disease; Animals; Antigens, Bacterial; Bacterial Outer Membrane Proteins; Bacterial Proteins; Cell Line; Cells, Cultured; Chaperonin 60; Chaperonins; Chronic Disease; Concanavalin A; Cytokines; Escherichia coli; Escherichia coli Infections; Female; Interferon-gamma; Interleukin-1; Interleukin-2; Interleukin-4; Macrophages, Peritoneal; Mice; Mice, Inbred BALB C; Phytohemagglutinins; Porins; Pyelonephritis; Spleen; Th1 Cells; Thymus Gland

We previously reported that interferon-gamma (IFN-gamma) production by PBMC in response to HCV core protein was increased in patients with type C chronic liver disease. To understand better the pathophysiology of this disease, we evaluated production of IL-10 and IL-12 by PBMC from 41 patients with chronic HCV infection, including asymptomatic HCV carriers with persistently normal serum ALT values. IL-10 is known to inhibit many effector functions of the immune system, suppressing Th1-type cell development, while IL-12 stimulates differentiation of Th1-type cells, facilitating cell-mediated immunity. IL-10 production was determined by culturing lymphocytes with concanavalin A (Con A), while IL-12 was produced by monocytes in the presence of Staphylococcus aureus Cowan 1 (SAC) with or without recombinant HCV core protein, respectively. The cytokine levels in culture supernatants were measured by ELISA. Spontaneous IL-10 production was greater in patients with chronic hepatitis (CH) (229 +/- 119 pg/ml, P < 0.01) and liver cirrhosis (LC) (185 +/- 88 pg/ml, P < 0.05) than in controls (119 +/- 27 pg/ml), while it was decreased during IFN treatment (70 +/- 25 pg/ml). Both HCV core protein and Con A enhanced IL-10 production by cells from HCV-infected patients. IL-12 was not detectable in medium alone cultures, and SAC-induced IL-12 production did not differ between various patient groups and controls. Simultaneous addition of HCV protein resulted in an increase of IL-12 production in chronic liver disease compared with SAC-alone cultures. Addition of IL-10 to the cultures equally suppressed IFN-gamma production for both controls and patient groups, but the enhancing effect of IL-12 on IFN-gamma production was significantly less in LC than in controls and other patient groups. The findings suggest that secretion of IL-10/IL-12 by cells from control individuals and various patient groups may be different, and that the cytokines might show different effects on IFN-gamma production by some cells.

Topics: Adult; Aged; Cells, Cultured; Chronic Disease; Concanavalin A; Female; Hepacivirus; Hepatitis C; Humans; Interferon-gamma; Interleukin-10; Interleukin-12; Leukocytes, Mononuclear; Male; Middle Aged; Viral Core Proteins

"Sho-saiko-to" (TJ-9) consists of 7 herbal components. In Japan, it is widely prescribed to patients with chronic viral liver disease. TJ-9 is known to suppress liver cancer development and possess macrobiotic effects, but its mode of action is not fully understood. This study investigated the following: 1) cytokine production levels, mainly interleukin (IL)-10, in peripheral blood mononuclear cells of chronic active hepatitis B and C patients, and healthy volunteers; 2) effects of TJ-9 on these productions; and 3) effects of each of its herb components on cytokine production in cell fractions. Results showed that without stimulants, IL-10 production in mononuclear cells of hepatitis B and C patients was significantly lower than that of healthy subjects (P < .01). IL-10 production induced by either phytohemagglutinin (PHA) or pokeweed mitogen (PWM) in mononuclear cells of hepatitis C patients were significantly lower than in patients with hepatitis B (P < .01) and healthy subjects (P < .05). IL-10 production induced by anti-CD3 or lipopolysaccharide (LPS) was significantly lower than in healthy subjects (P < .05). The addition of TJ-9 to the cultures strongly induced IL-10, and this induction was mainly attributable to the effects of 2 components (scutellaria root and glycyrrhiza root) on the monocyte/macrophage fraction. The production of IL-4 and IL-5 in cultures with concanavalin A (conA) was significantly higher in patients with hepatitis C than in the healthy subjects (P < .01; P < .05), but the addition of TJ-9 suppressed these increases by 25% to 33% (P < .01). Therefore, TJ-9 could adjust the decreased IL-10 production and the increased IL-4 and IL-5 production of mononuclear cells from patients with hepatitis C. Moderate regulation of the cytokine production system in patients with hepatitis C by using TJ-9 may be useful in the prevention of disease progression.

Topics: Adult; Aged; Cells, Cultured; Chronic Disease; Concanavalin A; Cytokines; Drugs, Chinese Herbal; Female; Hepatitis C; Humans; Interleukin-10; Lipopolysaccharides; Male; Middle Aged; Monocytes; Time Factors

In A/J (H-2a) (A) mice, the neonatal i.v. injection of (B10 x A)F1 spleen cells (SC) induces partial transplantation tolerance (TT) to C57BL/10ScSn (H-2b) (B10) skin allografts, chronic host-versus-graft disease (HVGD) and lethal lymphoproliferative disorders (LPD). They produce anti-T-cell autoantibodies (ATA), and the proliferative responses of their SC to the T cell mitogen Con A are decreased. We found that, similar to ATA, the hyporeactivity of T cells developed earlier (at 1-2 weeks of age) than splenomegaly. The proportions of both CD4+ and CD8+ T cells were not reduced in the spleens of tolerized mice without manifest LPD. The supernatants (SN) of Con A-stimulated tolerized SC contained no, or only small amounts of interleukin-2 (IL-2). Thus, in the tolerized mice, ATA and T cell deficiency preceded the development of LPD. ATA and the decreased amount of the T cell growth factor IL-2 might play a role in the defective T cell activation.

Topics: Age Factors; Animals; Animals, Newborn; Antigens; Autoantibodies; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Division; Cell Transplantation; Chronic Disease; Concanavalin A; Host vs Graft Reaction; Immune Tolerance; Interleukin-2; Lymphocyte Activation; Lymphocyte Count; Lymphoproliferative Disorders; Mice; Mice, Inbred A; Mice, Inbred C57BL; Mice, Inbred Strains; Mitogens; Skin Transplantation; Spleen; Splenomegaly; T-Lymphocytes; Transplantation Immunology

We have previously demonstrated that type I IFNs administered orally (p.o.) suppress clinical relapse in murine chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE), inhibit clinical attacks at doses equivalent to ineffective parenteral (s.c.) doses in acute rat EAE, and decrease the adoptive transfer of EAE. We therefore examined the optimal clinical p.o. dose of murine species-specific IFN-alpha for suppression of relapse attacks and compared it to s.c. administered IFN-alpha in a dose-response experiment in the chronic EAE model. The optimal clinically effective dose for suppression of EAE of p.o. administered murine species-specific IFN-alpha was 10 units and for s.c. administered was 100 units, although the optimal p.o. dose was much more clinically effective than the optimal s.c. dose. Con A- and MT-induced spleen cell proliferation was inhibited by p.o. IFN-alpha, as was Con A-induced IL-2 secretion, but s.c. IFN-alpha did not inhibit the Con A-induced proliferation in spleen cells. Oral IFN-alpha inhibited the mitogen-induced production of IL-2 and IFN-gamma, but s.c. IFN-alpha increased MT-induced IFN-gamma and IL-6 secretion in spleen cells and Con A-induced IL-6 and MT-induced IL-2 and IL-6 in lymph node cells. The oral route is a convenient drug delivery system that may allow the use of lower doses of cytokines and provide enhanced efficacy via unique and potent immunoregulatory circuits without generating additional inflammatory cytokines that may counteract the beneficial effects of s.c. administered type I IFNs.

Topics: Administration, Oral; Animals; Chronic Disease; Concanavalin A; Encephalomyelitis, Autoimmune, Experimental; Female; Injections, Subcutaneous; Interferon-alpha; Interferon-gamma; Interleukin-2; Interleukin-6; Lymph Nodes; Lymphocyte Activation; Mice; Mice, Inbred Strains; Mycobacterium tuberculosis; Spleen

Asthma and chronic bronchitis are associated with airway remodelling, and airway macrophages are present in bronchial inflammation. TGF-beta and fibronectin released by alveolar macrophages possess a fibrogenic potency. The potential role of alveolar macrophages in airway remodelling was studied in asthma and chronic bronchitis by the release of TGF-beta and fibronectin. Alveolar macrophages were isolated by bronchoalveolar lavage in 14 control subjects, 14 asthmatics and 14 chronic bronchitics. The spontaneous and lipopolysaccharide (LPS)- or concanavalin A (Con A)-induced release of TGF-beta and fibronectin was measured by ELISA. Alveolar macrophages from chronic bronchitics spontaneously release greater amounts of TGF-beta and fibronectin than those from asthmatic and control subjects. Alveolar macrophages from asthmatics release greater amounts of TGF-beta and fibronectin than those from control subjects. The spontaneous release of TGF-beta is significantly correlated with that of fibronectin. Fibronectin release was significantly reduced after LPS stimulation, and TGF-beta release was significantly increased after LPS stimulation, except in chronic bronchitis patients. Con A increased the release of TGF-beta in cells from normal subjects. This study suggests that activated macrophages play a role in airway remodelling in chronic bronchitis and to a lesser extent in asthma.

Topics: Adult; Asthma; Bronchitis; Chronic Disease; Concanavalin A; Female; Fibronectins; Humans; Lipopolysaccharides; Macrophages, Alveolar; Male; Middle Aged; Transforming Growth Factor beta

In an attempt to understand better the immunoregulatory disorders in paracoccidioidomycosis (PCM), the possible correlation between interleukin pattern, lymphoproliferation, C-reactive protein (CRP) and specific antibody levels was investigated in the polarized clinical forms of this disease. We studied 16 PCM patients, eight with the disseminated disease (four under treatment and four non-treated) and eight with the chronic disease. The patients with disseminated disease exhibited high antibody titres specific to Paracoccidioides brasiliensis antigen compared with patients with the chronic form of disease. Tumour necrosis factor (TNF), IL-1, IL-6 and CRP in the serum of non-treated disseminated PCM patients were increased, which correlated positively with the low mitogenic response of peripheral blood mononuclear cells (PBMC) to phytohaemagglutinin (PHA) (P < 0.01) and with the high antibody titres (P < 0.001) of these patients. Moreover, we found in the disseminated PCM patients positive correlations between IL-1 and IL-6 (P = 0.0007); IL-1 and TNF (P = 0.0045); IL-1 and IL-6 with the high antibody titres (P = 0.0834 and P = 0.0631, respectively); IL-1, IL-6 and TNF with CRP levels. By contrast, no correlations were found with those interleukins in the treated disseminated and chronic patients or in controls. It was interesting to find an inverse correlation between IL-4 and antibody production in non-treated disseminated PCM (r = -0.4770); moreover, a significant correlation (P = 0.0820) was found in chronic PCM patients with respect to the low level of either IL-4 and antibody titres against fungus antigen. Chronic PCM patients also had IL-2 levels inversely correlated with antibody production (r = -0.6313; P = 0.0628). Inverse correlations were also observed between IL-2 and IL-6 levels in non-treated disseminated patients (P = 0.0501) and between IL-2 and IL-4 in chronic patients (P = 0.0131). The inflammatory cytokines might have a pivotal role in the genesis and in control of some aspects of the disease, such as granulomatous reaction, hypergammaglobulinaemia and depression of T cell-mediated immunity in PCM.

Topics: Adult; Antibodies, Fungal; Antibody Specificity; C-Reactive Protein; Chronic Disease; Concanavalin A; Humans; Interleukins; Leukocytes, Mononuclear; Lymphocyte Activation; Male; Middle Aged; Paracoccidioidomycosis; Phytohemagglutinins; Stimulation, Chemical

In vitro and in vivo T cell responses were determined during the course of bronchopulmonary infection with mucoid Pseudomonas aeruginosa. T cell responses were compared in two inbred mouse strains, namely BALB/c mice, which are resistant to the establishment of chronic bronchopulmonary Ps. aeruginosa infection, and C57Bl/6 mice, which have high numbers of bacteria in the lungs through 14 days post-infection. Unseparated lung cells and lung T cells from BALB/c mice exhibited significantly higher in vitro proliferative responses to both heat-killed Ps. aeruginosa and concanavalin A (Con A) than cells from C57Bl/6 mice through 20 days post-intratracheal infection with 10(4) colony-forming units (CFU) Ps. aeruginosa. Proliferation of unseparated lung cells but not lung T cells from BALB/c mice infected 6 days previously with 10(5) CFU Ps. aeruginosa was suppressed in response to Con A; these cells were unresponsive to specific antigen. Suppression of lymphocyte proliferation in the lungs of C57Bl/6 mice infected with 10(4) CFU Ps. aeruginosa and in BALB/c mice infected with 10(5) CFU was found to be mediated by adherent lung cells via the production of nitric oxide and prostaglandins. Determination of in vivo T cell-mediated responses in infected mice demonstrated that resistant BALB/c mice had high DTH and low Pseudomonas-specific antibody responses, while C57Bl/6 mice had low DTH and high antibody levels, in particular, IgG2b and IgM.

Topics: Animals; Antibodies, Bacterial; Bronchial Diseases; Cell Division; Cells, Cultured; Chronic Disease; Concanavalin A; Disease Models, Animal; Female; Hypersensitivity, Delayed; Immunity, Cellular; Lung; Lung Diseases; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Pseudomonas Infections; T-Lymphocytes

We analyzed the Con A affinity of serum AFP in patients with a serum AFP concentration greater than 50ng/ml by antibody affinity electrophoresis and Western blotting to distinguish hepatocellular carcinoma (HCC) from benign chronic liver diseases (CLD). Of 164 patients with HCC, 48 (29.3%) had a single band, while 116 (70.7%) had multiple bands. All but three of 65 patients with cirrhosis had a single band. All but one of 32 patients with chronic hepatitis had a single band. We concluded that multiple AFP bands are diagnosis of HCC. This method is a useful assay for distinguishing HCC from CLD.

Topics: Adult; Aged; alpha-Fetoproteins; Blotting, Western; Carcinoma, Hepatocellular; Chronic Disease; Concanavalin A; Diagnosis, Differential; Electrophoresis, Agar Gel; Female; Hepatitis; Humans; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Sensitivity and Specificity

The response of IFN-gamma, IL-2 and IL-5 mRNA expression to the stimulation of concanavalin A (Con A) in peripheral blood mononuclear cells (PBMC) after bone marrow transplantation (BMT) was analyzed using reverse-transcriptase polymerase chain reaction (RT-PCR) to assess the recovery of T cell function. The subjects were 23 patients undergoing allogeneic BMT, 1 syngeneic BMT, 1 autologous BMT and 2 normal individuals. IFN-gamma mRNA expression increased after Con A stimulation in 6 patients who had limited chronic graft versus host disease (GVHD), 14 patients who did not have chronic GVHD, each one patient receiving syngeneic and autologous BMT and 2 normal individuals. On the other hand, IFN-gamma mRNA expression was not increased by Con A stimulation in 4 patients who had extensive chronic GVHD. Also, the concentration of IFN-gamma in cultured medium in a patient with extensive chronic GVHD was not detectable. A similar low response of IL-2 and IL-5 mRNA expression to Con A was observed in these patients with extensive chronic GVHD. These findings indicate that the cytokine productive capacity of T cell (IFN-gamma and IL-2 could be produced by type 1 T helper (Th1) cells and IL-5 could be produced by type 2 T helper (Th2) cells) was suppressed in patients who had extensive chronic GVHD, while that capacity was almost normal in patients without chronic GVHD and with limited chronic GVHD. Therefore, the analysis of cytokine gene response to Con A stimulation may provide useful information regarding immune reconstitution after BMT.

Topics: Adolescent; Adult; Base Sequence; Bone Marrow Transplantation; Chronic Disease; Concanavalin A; Cytokines; DNA Primers; Female; Gene Expression; Graft vs Host Disease; Humans; In Vitro Techniques; Interferon-gamma; Interleukin-2; Interleukin-5; Leukocytes, Mononuclear; Male; Molecular Sequence Data; Polymerase Chain Reaction; RNA, Messenger

The objective of this study was to ascertain whether immune abnormalities were present in a group of patients with chronic stable heart failure at a time when sympathetic drive was not excessive. Elevated sympathetic tone not only plays an important role in the pathophysiologic characteristics of congestive heart failure but may also regulate certain aspects of immune function, which has been shown to be abnormal in patients with severe heart failure. Studies have indicated a high incidence of heterophil antibodies against constituents of the heart, the presence of antibody-mediated cytotoxicity against cultured heart cells, and a decrease in suppressor and natural killer-cell function in patients with idiopathic dilated cardiomyopathy. Lymphocytes were separated over a Ficoll-Hypaque gradient. Lymphocyte subtypes and well as interleukin-2 receptors were detected by means of mouse monoclonal antibodies conjugated with fluorescein or phycoerytherin, and immunofluorescence was measured with a flow cytometer. Mitogen proliferation was assessed by tritiated thymidine incorporation in the presence of either conconavalin A or tetanus toxoid. Serum was used in conjunction with iodine 125-labeled iodopindolol binding to rat cardiac membranes to attempt to detect beta-receptor antibodies. In patients with ischemic (n = 21) and idiopathic (n = 16) cardiomyopathy, the norepinephrine levels were modestly elevated (idiopathic = 482 +/- 70 pg/ml; ischemic = 501 +/- 45 pg/ml) compared with control subjects without heart disease (n = 10; norepinephrine = 252 +/- 70 pg/ml). We found no differences in the number and subtypes of circulating lymphocytes in the three groups, and there was no serum inhibition of beta-binding to rat cardiac membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Chronic Disease; Concanavalin A; Heart Failure; Humans; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Middle Aged; Receptors, Adrenergic, beta; Receptors, Interleukin-2; T-Lymphocytes; Tetanus Toxoid

Altered interleukin 2 (IL-2) production has been implicated in the pathogenesis of inflammatory bowel diseases.. The temporal relationship between IL-2, prostaglandin E2 (PGE2) production, and mucosal injury was evaluated by isolated colonic lamina propria mononuclear cells (LPMC), using the trinitrobenzene sulfonic acid model of rat colitis.. Spontaneous LPMC IL-2 activity was significantly increased in chronic (5 weeks) but not acute (5 days) or resolved colitis groups. IL-2 activity after concanavalin A activation was highest in the groups with resolved and chronic colitis. PGE2 production was significantly increased in LPMC cultures in acute or chronic colitis as well as the ethanol control groups but not the resolved colitis group. The addition of indomethacin to LPMC cultures decreased PGE2 levels in all groups, whereas IL-2 activity increased only for the chronic and resolved colitis groups. No correlation was found between PGE2 and IL-2 production by LPMC.. In this experimental model, LPMC IL-2 production varied according to the severity and duration of the inflammation. Increased PGE2 production does not appear to be responsible for the IL-2 alterations in colitis.

Topics: Acute Disease; Animals; Chronic Disease; Colitis; Concanavalin A; Dinoprostone; Disease Models, Animal; Female; Inflammation; Interleukin-2; Intestinal Mucosa; Lymphocyte Activation; Lymphocytes; Organ Size; Rats; Rats, Sprague-Dawley; Reference Values; Spleen; Trinitrobenzenesulfonic Acid

Peripheral blood mononuclear cells (PBMC) from 25 patients with chronic hepatitis B were tested for the presence of free monomeric hepatitis B virus (HBV) DNA migrating as a single 3.2 Kb band by Southern blot analysis. The PBMC were cultured for 7 days in the presence of phytohemagglutinin (PHA) or concanavalin A (ConA) both of which yielded a proliferative response. By contrast, both bacterial lipopolysaccharide (LPS) and interleukin 2 (IL2) failed to do so. Dot blot assays were used to monitor HBV DNA level increase within PBMC. Following mitogen exposure HBV DNA levels increased above pre-stimulation levels in 19/25 PHA cultures, 6/15 ConA cultures, 1/15 LPS cultures, and 1/15 IL2 cultures. In 15 patients, Southern blot analysis was carried out before and after PHA exposure. In 13/15 cases, a single 3.2 Kb band was observed in unstimulated cultures as well as in PHA cultures even though PHA induced a HBV DNA increase. One case exhibited bands migrating faster than the 3.2 Kb signal, compatible with replicating intermediates and one case provided evidence of viral concatemers within PBMC after PHA stimulation. No HBV DNA was detected in the culture supernatants. The increase of HBV DNA level in PBMC induced by mitogen was strongly associated with an increase in HBV DNA expression (HBV RNA and HBs antigen). These studies indicate that HBV DNA present in human PBMC does represent a potential reservoir for infection with endogenous reactivation following PBMC activation.

Topics: Blotting, Southern; Chronic Disease; Concanavalin A; Culture Media; DNA, Viral; Female; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Interleukin-2; Leukocytes, Mononuclear; Lipopolysaccharides; Male; Mitogens; Phytohemagglutinins; RNA, Viral

Microheterogeneity of acute phase proteins frequently differs in acute and chronic types of inflammation. However, it is unknown whether these changes depend on the duration of the inflammation in a given disease. We therefore investigated the microheterogeneity of alpha 1-acid glycoprotein (AGP) in sera from patients with acute and chronic bacterial infection in comparison to rheumatoid arthritis and ankylosing spondylitis. In acute bacterial infection Con A-reactivity of AGP was significantly elevated. By contrast, AGP in chronic bacterial infection showed the same glycosylation pattern as rheumatoid arthritis and ankylosing spondylitis being characterized by a decreased reactivity to Con A. Serial measurements in individual patients with bacterial infections showed a transition from the initially elevated to decreased reactivity to Con A as the disease became chronic.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Bacterial Infections; C-Reactive Protein; Chronic Disease; Concanavalin A; Female; Glycosylation; Humans; Immunoelectrophoresis, Two-Dimensional; Male; Middle Aged; Orosomucoid; Spondylitis, Ankylosing; Staphylococcal Infections; Streptococcal Infections

Both acute and chronic restraint stress modulated mitogen-induced increases in cytoplasmic free-calcium concentrations ([Ca2+]i) in mouse spleen cells. Dual-color analysis of lymphocyte subpopulations demonstrated that acute (2 hour) restraint stress suppressed mitogen-stimulated increases in [Ca2+]i in CD4+ T cells, but enhanced [Ca2+]i in CD8+ T cells. Chronic restraint stress (2 hours daily for up to 21 days) resulted in a significant suppression of mitogen-stimulated increases in [Ca2+]i in CD4+ T cells at 3 and 7 days, but not at 21 days. CD8+ T cells were unaffected by chronic stress. Chronic stress (for 7 days) had a modest suppressive effect on mitogen-induced Ca2+ responses in B cells. Within T lymphocyte subpopulations, both acute and chronic stress predominantly affected CD4+ T cells, which may induce a functional reversal of the CD4/CD8 ratios in vivo. Such a reversal could result in suppression of a variety of immune responses such as lymphocyte proliferation and antigen-specific antibody production. These findings indicate that the inhibitory effects of stress on calcium mobilization in lymphocytes may be an early event mediating stress-induced immunosuppression.

Topics: Acute Disease; Animals; B-Lymphocytes; Calcium; Chronic Disease; Concanavalin A; Corticosterone; Immobilization; Immunosuppression Therapy; Kinetics; Lymphocyte Activation; Male; Mice; Mice, Inbred C57BL; Spleen; Stress, Physiological; T-Lymphocytes

T-cell suppression induced by concanavalin-A (Con-A) and the prostaglandin suppressor system (PSS) were studied in 14 patients with pigeon breeder's disease (PBD), 12 and 10 asymptomatic breeders, and 8 controls. Our results showed that PBD patients display a significant decrease in T-cell-induced suppression (29.6 +/- 15.3% vs. 61.2 +/- 9.3% in controls p less than 0.05); whereas asymptomatic breeders respond heterogeneously: 5 showed decreased suppression and 7 were within the normal range obtained in controls. In contrast, the patients presented a higher PSS index compared with the other 2 groups, suggesting an inverse relationship between the 2 systems. These findings indicate that there are relevant differences between PBD patients, asymptomatic breeders, and normal subjects in some immune interactions, which may at least partially explain the characteristic cellular and humoral hyperreactivity observed in patients with this disease.

Topics: Adult; Alveolitis, Extrinsic Allergic; Animals; Bird Fancier's Lung; Chronic Disease; Columbidae; Concanavalin A; Female; Humans; Leukocytes, Mononuclear; Lymphocyte Activation; Male; Prostaglandins; T-Lymphocytes, Regulatory

Serum samples from 20 patients with acute exacerbation of chronic hepatitis due to hepatitis B virus and 20 patients with hepatocellular carcinoma arising from B viral cirrhosis with elevated levels of alpha-fetoprotein (AFP) were analyzed by affinity column chromatography for concanavalin A binding. Serum AFP was tested at regular intervals in all of these patients. Acute exacerbation was defined as elevation of serum transaminase greater than 300 IU/L in patients with chronic hepatitis B. In hepatocellular carcinoma, serum AFP levels fluctuated but remained higher than 92 ng/ml, whereas, in acute exacerbation of chronic hepatitis B, serum AFP levels returned to normal within 3-12 months of follow-up. The results of concanavalin A-binding assay revealed that AFP from both these groups had a high affinity for concanavalin A, and this assay could not be used to discriminate between the two conditions.

Topics: Adult; Aged; alpha-Fetoproteins; Carcinoma, Hepatocellular; Chromatography, Affinity; Chronic Disease; Concanavalin A; Diagnosis, Differential; Female; Follow-Up Studies; Hepatitis B; Humans; Liver Neoplasms; Male; Middle Aged

Suppressor T-cell activity and allogeneic T-cell response to concanavalin A (ConA) were investigated in 46 patients chronically infected with hepatitis B virus (HBV). Thirty-eight patients had chronic active hepatitis, seven of whom were superinfected with Delta virus, and eight were healthy chronic HBV carriers. T-cell suppressor activity was in the normal range in healthy carriers and in patients negative for serum HBV-DNA, independent of the e antigen status. In contrast, the group of patients positive for HBV-DNA exhibited a significant reduction in suppressor activity. Longitudinal studies in patients who cleared serum HBV-DNA demonstrated that suppressor T-cell activity became normal thereafter. These results suggest a relationship between suppressor T-cell function and the stage of viral replication in individuals with chronic HBV infection.

Topics: Adult; Aged; Carrier State; Chronic Disease; Concanavalin A; DNA Replication; DNA, Viral; Female; Hepatitis B; Hepatitis B virus; Hepatitis, Chronic; Humans; Immunity, Cellular; Longitudinal Studies; Lymphocyte Activation; Male; Middle Aged; T-Lymphocytes, Regulatory; Virus Replication

Effect of hemodialysis (HD) on some indices of immune response was studied in nine chronic uremics. Total lymphocyte, OKT4+, and OKT8+ cell numbers significantly decreased during the first 20 min of HD, and they were decreased till the third hour of the procedure, whereas the OKT4+/OKT8+ cell number ratio did not change significantly. Before HD, Con-A--activated suppressor cells exerted a stimulatory action on autologous responder cells measured in two-step culture. During HD, Con-A-activated suppressor cell activity transiently appeared, with its peak at 60 min after the start of HD. It was accompanied by a transient rise in lymphocyte count with spontaneous interleukin-2 (IL-2) receptor expression, whereas the number of cells expressing IL-2 receptor following phytohemaglutinin (PHA) stimulation was progressively decreased during HD. A significant correlation was found between the increment of Con-A-activated suppressor cell activity and the increment of spontaneous IL-2 receptor expression on lymphocytes during one single blood flow through the dialyzer. The results supply further evidence that HD may impose additional disturbances on immune regulation in chronic uremics.

Topics: Adult; Chronic Disease; Concanavalin A; Female; Humans; Leukocyte Count; Lymphocyte Activation; Male; Receptors, Interleukin-2; Renal Dialysis; T-Lymphocytes; T-Lymphocytes, Regulatory; Uremia

Topics: Carcinoma, Hepatocellular; Chronic Disease; Concanavalin A; Diagnosis, Differential; Electrophoresis; Electrophoresis, Cellulose Acetate; gamma-Glutamyltransferase; Hepatitis; Humans; Isoenzymes; Liver Cirrhosis; Liver Neoplasms; Octoxynol; Polyethylene Glycols; Sensitivity and Specificity

Humoral and cellular immune responses were measured during the progression of chronic pulmonary and disseminated paracoccidioidomycosis in mice. The chronic disease was established by pulmonary infection of mice with different doses of the yeast form of Paracoccidioides brasiliensis isolate GAP. Levels of antibodies to P. brasiliensis, detected in serum by immunodiffusion and enzyme-linked immunosorbent assay, directly correlated with the size of the infectious challenge. Significant delayed-type hypersensitivity (DTH) responses to antigen were largely restricted to week 1 after pulmonary infection with intranasally administered high doses (5.0 x 10(6) or 1.1 x 10(7) CFU per inoculum). In vitro lymphoproliferative responses of peripheral blood lymphocytes (PBL) to P. brasiliensis antigens were significant only at 2 weeks after infection with intranasally administered 1.1 x 10(7) CFU. Responses of PBL to concanavalin A were depressed (50% of control response) as early as 8 weeks and reached a nadir at 10 to 18 weeks after infection. Infected mice made antibodies to sheep erythrocytes (SRBC) (10(9) intravenously [i.v.]) normally at all times tested after infection. In contrast, infected mice sensitized to SRBC (10(6) i.v.) had significantly depressed DTH responses to SRBC at 9 and 20 weeks postinfection compared with noninfected mice. These results indicated that in this model, normal humoral responses developed to homologous and heterologous antigens. In contrast, the T cellular immune responses were depressed with progression and chronicity of the disease. Thus, this model closely mimics the immunological findings in human paracoccidioidomycosis.

Topics: Animals; Antibodies, Fungal; Antigens, Fungal; Blood Group Antigens; Chronic Disease; Coccidioidomycosis; Concanavalin A; Enzyme-Linked Immunosorbent Assay; Hypersensitivity, Delayed; Immunity, Cellular; Immunodiffusion; Lung Diseases, Fungal; Lymphocyte Activation; Male; Mice; Mice, Inbred BALB C; Sheep

Immunosuppression is a well-characterized consequence of chronic graft-versus-host disease (GVHD). We have previously shown that interferon (IFN) is produced in high levels during acute GVHD. Our objective in this study was to determine if IFN, as a cytokine with known immunosuppressive qualities, could be detected in mice experiencing chronic GVHD-induced immunosuppression. Two different experimental models were used to induce chronic GVHD. The first model involved the injection of parental strain spleen cells into adult F1 hybrids (AJ----B6AF1), while the second model utilized GVHD induced across minor histocompatibility barriers (B10.D2----BALB/c). Results indicated that significant levels of serum IFN-alpha/beta are present in mice undergoing chronic GVHD. Spleen cells from chronic GVHD mice were also shown to produce significant levels of IFN-alpha/beta upon in vitro culture in medium only. This IFN-alpha/beta production was greatly increased when GVHD spleen cells were cultured with either concanavalin A (Con A) or IL-2. In contrast, IFN-gamma production was undetectable in these Con A- or IL-2-containing cultures. Additionally, these same spleen cells which produced high levels of IFN-alpha/beta were immunosuppressed as measured by mitogen-induced cell proliferation. These results suggest that IFN-gamma production is defective in GVHD spleen cells, and that the presence of high IFN-alpha/beta production by GVHD mice may contribute to the immunosuppression associated with chronic GVHD.

Topics: Acute Disease; Animals; Bone Marrow Transplantation; Cells, Cultured; Chronic Disease; Concanavalin A; Female; Graft vs Host Disease; Immune Tolerance; Interferon Type I; Interferon-gamma; Interleukin-2; Lymphocyte Activation; Mice; Mice, Inbred Strains; Spleen

We investigated some aspects of the regulation of the immune response that were sensitive to the effect of indomethacin, an inhibitor of prostaglandin synthesis, in two groups of patients in the chronic phase of Chagas' disease, and in normal controls. One group of patients was defined as being infected but with no clinical evidence of cardiac involvement, while the other showed electrocardiographic alterations that are characteristic of Chagasic cardiomyopathy. The in vitro responses to mitogens (phytohemagglutinin and concanavalin A) and Trypanosoma cruzi antigens were evaluated in the presence or absence of indomethacin. It was found that the in vitro mitogenic stimulation by both phytohemagglutinin and concanavalin A of peripheral blood mononuclear cells from normal controls and infected and cardiomyopathic patients was significantly increased by indomethacin. An inverse correlation was found between the initial response to concanavalin A and the subsequent increase caused by the presence of indomethacin, for both the patients and the controls. Considering specific responses to T. cruzi antigens, we showed that in the presence of indomethacin these were significantly increased in infected patients, but not in cases of cardiomyopathy. Again, a significant inverse correlation was found between the basal responsiveness and the indomethacin-induced change. In general, infected patients showed changes in the presence of indomethacin that were most comparable to those of normal individuals. It would appear, therefore, that normal indomethacin-sensitive (prostaglandin-dependent) suppressor mechanisms operate in Chagas' patients. In certain cardiomyopathy patients, however, these control mechanisms may not operate; a possible consequence of this could be tissue damage.

Topics: Animals; Chagas Disease; Chronic Disease; Concanavalin A; Female; Humans; Indomethacin; Lymphocyte Activation; Male; Phytohemagglutinins; Reference Values; Trypanosoma cruzi

1. The ability of peripheral blood mononuclear cells (PBMC) from Chagas' disease patients to induce monocyte procoagulant activity (PCA) in response to concanavalin A (Con A) and to a Con A induced lymphokine was studied. 2. In spite of the variability of PCA levels among both chagasic patients and normal controls, statistical analysis of the data permitted us to draw the following general conclusions. 3. The Con A-induced monocyte PCA measured in 17 assays of 15 chagasic patients was significantly lower than the PCA response of 18 normal controls or of 11 patients with non-chagasic myocardiopathies. 4. The response of PBMC from chagasic patients to lymphokine was also lower than that observed for normal controls. 5. These results suggest that monocytes from chagasic patients are deficient for the generation of PCA which is an in vitro correlate of the delayed-type hypersensitivity reaction.

Topics: Adult; Animals; Blood Coagulation; Blood Coagulation Factors; Chagas Cardiomyopathy; Chronic Disease; Concanavalin A; Female; Humans; Lymphokines; Male; Middle Aged; Monocytes; Trypanosoma cruzi

Peripheral blood mononuclear cells (PBMC) from strain 13 guinea pigs at various stages of chronic relapsing experimental allergic encephalomyelitis (CREAE) showed significantly reduced reactivity to the polyclonal T cell mitogens, phytohaemagglutinin and concanavalin A. Serum taken at the same time revealed an increase in inhibitors of lymphocyte mitogenesis. The factors identified appeared to inhibit the initial stages of lymphocyte proliferation: they were not cytotoxic for lymphocytes nor were they complement-dependent.

Topics: Animals; Chronic Disease; Concanavalin A; Encephalomyelitis, Autoimmune, Experimental; Guinea Pigs; Lymphocyte Activation; Phytohemagglutinins

Abnormal T-cell regulation of lymphocyte proliferation may contribute towards tissue damaging mechanisms in chronic liver disease. We therefore studied Concanavalin A induced suppressor cell activity in T-T interaction in 47 patients with chronic liver disease, using both an autologous and an allogeneic system. In the autologous system, no differences were found between those with auto-immune chronic active hepatitis, HBsAg positive chronic active hepatitis, primary biliary cirrhosis, alcoholic liver disease and normal controls. However, several abnormalities were identified in allogeneic cultures with normal lymphocytes which allowed separate analysis of the influence of suppressor and responder cells from patients with chronic liver disease. An abnormality of the suppressor population was found in those with autoimmune chronic active hepatitis, primary biliary cirrhosis and alcoholic liver disease, while the responder population was abnormal in those with autoimmune or HBsAg positive CAH. Failure to demonstrate an abnormality in an autologous system may reflect a combined defect of suppressor and responder populations, and in this study the allogeneic system was a more sensitive index of abnormal cellular T-T interaction.

Topics: Autoimmune Diseases; Chronic Disease; Concanavalin A; Hepatitis B Surface Antigens; Humans; Liver Diseases; Lymphocyte Activation; T-Lymphocytes, Regulatory

Autologous transfusions of 111indium-labelled peripheral blood lymphocytes reportedly image the pancreas of patients with Type 1 (insulin-dependent) diabetes at the time of onset. We attempted to apply this technique to the spontaneously diabetic BB/W rat. First, acutely diabetic BB/W rats, diabetes-prone BB/W rats, diabetes-resistant W-line BB/W rats, and Wistar Furth rats were given autologous transfusions of labelled peripheral blood lymphocytes. Radioactivity recovered from the pancreas was similar in all groups. No correlation was found between the intensity of imaging and the presence or intensity of insulitis. To decrease non-specific intravascular radioactivity, acutely diabetic, diabetes-prone, and W-line rats were perfused 48 h after autologous transfusion of labelled lymphocytes. Again, the intensity of recovered activity was similar in all groups, using both macroautoradiography and numerical counting techniques. A second set of experiments studied diabetes and insulitis induced by passive transfer of concanavalin A-treated splenic lymphocytes from acutely diabetic donors. Activated lymphocytes were labelled with 111Indium and given to groups of diabetes-prone and diabetes-resistant rats. There were no differences in pancreatic localization 72-96 h after injection. Groups of diabetes-prone and diabetes-resistant rats were also given concanavalin A-activated lymphocytes and then challenged 2-10 days later with autologous transfusions of labelled peripheral blood lymphocytes. Again, no differences in organ labelling or imaging were detected. We conclude that the autologous transfusions of 111indium-labelled lymphocytes do not label or image the pancreas of the BB/W rat.

Topics: Acute Disease; Animals; Chronic Disease; Concanavalin A; Diabetes Mellitus, Experimental; Indium; Lymphocyte Activation; Lymphocytes; Mathematics; Pancreas; Perfusion; Radioisotopes; Radionuclide Imaging; Rats; Rats, Inbred WF; Time Factors

Topics: Adolescent; Child; Child, Preschool; Chronic Disease; Concanavalin A; Glomerulonephritis; Humans; Lymphocyte Activation; Nephrotic Syndrome; Receptors, Fc; Rosette Formation; T-Lymphocytes, Regulatory

Twenty-seven patients with chronic obstructive bronchitis and 47 patients with chronic non-obstructive bronchitis were subjected to subpopulation analysis of peripheral blood immunocompetent cells. Statistically significant changes in the content of T mu and T gamma cells, killer and suppressor activity of lymphocytes were discovered in patients with chronic bronchitis. One of the immunological differences between chronic obstructive and chronic non-obstructive bronchitis lies in the activity of Con A-induced suppressors, which is appreciably lowered in patients with chronic obstructive bronchitis.

Topics: Adjuvants, Immunologic; Adolescent; Adult; B-Lymphocytes; Bronchitis; Chronic Disease; Concanavalin A; Drug Evaluation; Humans; Ketotifen; Leukocyte Count; Levamisole; Middle Aged; Prodigiozan; T-Lymphocytes

Patients with acute hepatitis B and HBV-induced chronic hepatitis as well as normal control persons participated in the study. Hepatitis patients of both groups have decreased OKT4+/OKT8+T cell ratios due to an percental increase of OKT8+T cells in peripheral blood compared to the data of controls. Lymphocyte cultures of chronic hepatitis patients show reduced DNA synthesis after stimulation by allogeneic non-T cells, PHA, Con A and PWM. PWM-induced immunoglobulin secretion by B cells, determined by means of a reverse haemolytic plaque assay (RHPA) and a solid phase ELISA, showed comparable results in hepatitis B patients and controls. The AMLR, which is thought to reflect an autologous immunoregulatory phenomenon, is slightly impaired in cultures of hepatitis B patients in comparison to controls. Con A-induced suppressor cell activity on T cell reactions is decreased in hepatitis, whereas suppressor cell activity on B cell activation is within the same range as in cultures of controls. It is concluded from these data, that suppressor cell activity on T cell function is impaired in hepatitis B, whereas B cell functions and suppressor cell activity on B cell function are in the normal range. The results with the functional assays and the finding of increased proportions of OKT8+T cells in hepatitis B are considered to reflect properties of different T cell subpopulations, responsible for different immunoregulatory functions.

Topics: Acute Disease; Chronic Disease; Concanavalin A; Hemolytic Plaque Technique; Hepatitis B; Humans; Immunoglobulins; Leukocyte Count; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; T-Lymphocytes; T-Lymphocytes, Regulatory

Lymphocyte suppressive activity after stimulation with Con A and lymphocyte function as the effectors in the ADCC test had been examined in 68 patients with chronic glomerulonephritis (GN) and in 20 healthy controls. Lymphocyte suppressive activity was lower in patients with chronic GN than in the healthy individuals. In regard to chronic proliferative GN and mesangial GN the difference was statistically significant. The lymphocyte efficiency in the ADCC test was generally adequate in patients with chronic GN and none of the morphological types showed significant deviation from the control group. In the general analysis of patients with chronic proliferative, mesangial, membrano-proliferative and membranous GN a decrease of lymphocyte suppressive activity below the lower standard limit has been detected (45% of cases). A similar defect in lymphocyte function in the ADCC test has been found in 18.6%. A statistically significant relationship between the lymphocyte function disorders and the high clinical dynamism of GN has been noticed, although in some cases there was a deviation from this tendency. It is supposed that circulating immune complexes, detected in some patients with chronic GN are not the only decisive factors responsible for defects in lymphocyte function.

Topics: Adult; Antibody-Dependent Cell Cytotoxicity; Chronic Disease; Concanavalin A; Female; Glomerulonephritis; Humans; Lymphocytes; Male; Middle Aged; T-Lymphocytes, Regulatory

Peripheral blood B cell response to staphylococcus aureus (SpA) Cowan I was evaluated in 8 healthy subjects, 8 patients with liver cirrhosis (LC), and 2 patients with chronic active hepatitis (CAH) with hypergammaglobulinemia (greater than 2 g/dl). In control studies it was shown that stimulation by SpA Cowan I was much less T cell-dependent than that induced by pokeweed mitogen (PWM) or con-canavalin A (ConA) when the amounts of immunoglobulins (Ig) secreted into culture supernatants were measured by radioimmunoassay (RIA) and the blastogenic response was measured by incorporation of tritiated thymidine. B cells from only 2 patients revealed increased Ig synthesis by SpA Cowan I stimulation. In the study of blastogenic response, increased DNA synthesis of B cells by SpA Cowan I stimulation was observed in 2 patients and decreased DNA synthesis in 3 patients. The remaining patients demonstrated normal range response. There was no correlation between B cell response to SpA Cowan I and clinical data such as gammaglobulin level in the patients studied. These studies indicate that B cell function remains intact in many patients with chronic liver disease with hypergammaglobulinemia.

Topics: Adult; Aged; B-Lymphocytes; Chronic Disease; Concanavalin A; Female; Hepatitis, Chronic; Humans; Immunoglobulin G; Immunoglobulin M; Liver Cirrhosis; Lymphocyte Activation; Male; Middle Aged; Pokeweed Mitogens; Staphylococcus aureus

Topics: Adult; Aged; alpha-Fetoproteins; Chronic Disease; Concanavalin A; Female; Ferritins; Hepatitis B; Humans; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Diseases; Liver Neoplasms; Male; Middle Aged

Suppressor cell activity (SCA) was analyzed in 8 patients with idiopathic membranous nephropathy (MN) and in 11 patients with chronic proliferative glomerulonephritis (CGN). We have assessed the ability of peripheral blood lymphocytes (PBL) stimulated by concanavalin A (Con A) to inhibit the proliferative response on normal allogenic lymphocytes by both Con A and phytohemagglutinin (PHA). It was found that the MN patients with nephrotic syndrome (NS) had significantly increased levels of suppression index (SI) when compared to the values obtained with normal controls. In contrast, the mean suppression values in the PBL from MN patients in remission and CGN patients with or without NS, whether the mitogen used was Con A or PHA, were similar to those of the control subjects. Thus, the majority of MN patients wih NS demonstrated an alteration in Con-A-induced SCA. The possible significance of these phenomena in the pathophysiology of MN is discussed.

Topics: Adult; Chronic Disease; Concanavalin A; Dose-Response Relationship, Immunologic; Female; Glomerulonephritis; Humans; Immunoglobulin A; Lupus Erythematosus, Systemic; Lymphocyte Activation; Male; Middle Aged; T-Lymphocytes, Regulatory

Suppressor cell activity (SCA) was analyzed in 8 patients with focal glomerular sclerosis (FGS) and 11 patients with chronic proliferative glomerulonephritis (CGN). We have assessed the ability of peripheral blood lymphocytes (PBL) stimulated by concanavalin A (Con A) to inhibit the proliferative response of normal allogeneic lymphocytes by both Con A and phytohemagglutinin (PHA). It was found that the FGS patients with nephrotic syndrome (NS) had significantly increased levels of suppression index when compared to the values obtained with normal controls. In contrast, the mean suppression values in the PBL from FGS patients in remission and CGN patients with or without NS, whether the mitogen used was Con A or PHA, were similar to those of the control subjects. Thus, the majority of FGS patients with NS demonstrated an alteration in Con A-induced SCA. The possible significance of these phenomena in the pathophysiology of FGS is discussed.

Topics: Adolescent; Adult; Chronic Disease; Concanavalin A; Female; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Humans; Male; Middle Aged; Nephrotic Syndrome; Phytohemagglutinins; T-Lymphocytes, Regulatory

Topics: Adolescent; Adult; Chronic Disease; Concanavalin A; Female; Glomerulonephritis; Humans; Lupus Erythematosus, Systemic; Male; Middle Aged; Phytohemagglutinins; T-Lymphocytes, Regulatory

Antigen-stimulated peripheral blood mononuclear cells from 14 patients with chronic Chagas' disease were examined for their ability to generate soluble factor(s) capable of activating human macrophages to a microbicidal state. Mononuclear cell factors (MCF) from all but one patient were capable of inducing macrophages to a state where they were able to kill trypomastigotes of Trypanosoma cruzi. Macrophage microbicidal activity against this organism was nonspecific, because it could be induced by lymphokine from PPD-positive subjects exposed to heat-killed BCG or by concanavalin A stimulation of normal donors cells. A factor(s) generated by the stimulation of mononuclear cells from normal donors by T. cruzi antigen did not induce macrophage microbicidal activity. Opsonization of the organisms with specific IgG did not alter their fate in normal macrophages, but enhanced their killing in MCF-activated cells. Induction of macrophage activation in the human system differed from the results previously described in mice in a few features: 1) Optimal microbicidal activity did not require daily addition of the soluble factors. 2) The MCF dose-response curve was shifted to lower concentrations. 3) MCF activity generated by antigen-stimulated peripheral blood lymphocytes correlates with their proliferative responses to antigen. Half of the patients showed low proliferative responses and correspondingly lower MCF activity. Mitogen responses were normal in all patients. No correlation was found between low or high responses and clinical manifestations of disease.

Topics: Animals; BCG Vaccine; Blood Proteins; Cells, Cultured; Chagas Disease; Chronic Disease; Concanavalin A; Humans; Immunoglobulin G; Lymphocyte Activation; Macrophages; Mice; Mice, Inbred A; Monocytes; Phagocytes; Receptors, Fc; Time Factors; Trypanosoma cruzi

During the course of adjuvant arthritis in rats adherent spleen cells inhibited the response of spleen lymphocytes to the T-cell mitogen concanavalin A (Con A). The effects of 14 days treatment with various antirheumatic drugs on spleen cell responsiveness to Con A were investigated. Two nonsteroidal anti-inflammatory drugs, indomethacin (1 mg/kg/day p.o.) and acetylsalicylic acid (200 mg/kg/day p.o.) did not modify the spleen cell response, whereas treatment with chloroquine (50 mg/kg/day p.o.) or levamisole (5 mg/kg/day p.o.) further increased the inhibitory effects of the adherent suppressive spleen cells. On the contrary, treatment with sodium aurothiomalate (10 mg/kg/day i.m.), D-penicillamine (50 mg/kg/day p.o.) or pyritinol (50 mg/kg/day p.o.) significantly enhanced the response of the lymphocytes to Con A. In addition to the effects on spleen cell responsiveness, the ability of the various drug treatments to modify the polyarthritic lesions of the disease was investigated. It is suggested that this model may provide a valuable approach for evaluating the effects of antirheumatic drugs in vivo on immunological responsiveness during chronic inflammatory disease.

Topics: Animals; Anti-Inflammatory Agents; Aspirin; Chloroquine; Chronic Disease; Concanavalin A; Female; Gold Sodium Thiomalate; Indomethacin; Inflammation; Levamisole; Penicillamine; Rats; Rats, Inbred Strains; Spleen

Total serum ferritin and the proportion of serum ferritin binding to concanavalin A (glycosylated ferritin) was measured in 18 healthy volunteers and in 84 patients, eight with primary haemochromatosis, 43 with beta-thalassaemia major and secondary iron overload and 33 with chronic liver diseases without iron overload. The total serum ferritin was either equally or even more closely related than either the non-binding or the concanavalin A binding ferritin, to the liver iron concentration in all patients with iron overload, and with the units of blood transfused in non-chelated thalassaemic patients. The total serum ferritin showed a significant correlation with serum aminotransferase for the group of 84 patients. In the thalassaemic patients the ferritin binding to concanavalin A also correlated with aminotransferase. However, in the other groups it was the ferritin not binding to concanavalin A which showed a significant correlation with aminotransferase activity. These results suggest that measuring the fraction of serum ferritin which binds to concanavalin A does not offer any advantage over estimation of the total serum ferritin concentration in the assessment of iron stores in patients wit iron overload and liver damage.

Topics: Binding Sites; Chronic Disease; Concanavalin A; Ferritins; Hemochromatosis; Humans; Iron; Liver; Liver Diseases; Thalassemia; Transaminases

Cell-mediated immune response was evaluated in 14 children with long-lasting intra- or extrahepatic cholestasis. Cell-mediated immunity was clearly depressed in children with intrahepatic cholestasis while children with extrahepatic biliary obstruction had a more modest and variable degree of impairment. This finding may be related to the longer duration of cholestasis and the higher total bile acid level in the intrahepatic compared to the extrahepatic group. In particular, in children with Byler disease, long-lasting, severe intrahepatic cholestasis was associated with depressed cell-mediated immunity and recurrent severe infections.

Topics: Adolescent; Child; Child, Preschool; Cholestasis; Chronic Disease; Concanavalin A; Female; Humans; Hypersensitivity, Delayed; Immunity, Cellular; Infant; Lymphocyte Activation; Lymphocytes; Male; Phytohemagglutinins; Rosette Formation; Skin Tests

Topics: Adult; Animals; Chronic Disease; Concanavalin A; Female; Hepatitis; Humans; Immunoglobulin Fc Fragments; Lupus Erythematosus, Systemic; Male; Middle Aged; Phytohemagglutinins; T-Lymphocytes; T-Lymphocytes, Regulatory

Suppressor T cell activity was studied serially in 11 patients with HBsAg-negative chronic active hepatitis when the disease was clinically and histologically inactive and during relapse using a short-lived suppressor cell assay. With a concentration of concanavalin A which gave a suboptimal proliferative response in normal subjects, the expected increase in thymidine incorporation was seen when the addition of the mitogen was delayed for 24 hr after the start of the lymphocyte culture period, a finding consistent with the disappearance of functional suppressor cells during the initial incubation. This effect was seen both in normal subjects and in patients with inactive disease, but was not observed at times of relapse. Further studies revealed a marked increase in lymphocyte sensitivity to concanavalin A at these times, a finding which might explain the apparent decrease in suppressor cell activity. When lower concentrations of mitogen were used in the assay, however, a significant reduction in suppressor cell activity was observed in the patients with chronic active hepatitis which was almost equal in magnitude in both the active and inactive groups, suggesting the presence of a true suppressor cell defect in this disease.

Topics: Adolescent; Adult; Chronic Disease; Concanavalin A; Dose-Response Relationship, Immunologic; Female; Hepatitis; Humans; Lymphocyte Activation; Male; Middle Aged; T-Lymphocytes, Regulatory

Topics: Chronic Disease; Concanavalin A; Hepatitis; Humans; Immune Tolerance; T-Lymphocytes, Regulatory

We investigated lymphocyte suppressor cell activity in 53 patients with acute and chronic liver diseases. Suppressor cells were generated by preincubation of peripheral blood mononuclear cells (PBM) with concanavalin A (Con A) for 48 hr. Suppressor cell activity was evaluated by inhibition of Con A-stimulated blast transformation and by inhibition of pokeweed mitogen-induced immunoglobulin (Ig) synthesis of fresh allogeneic normal PBM in the second-set cultures. Of 29 patients with chronic active liver diseases (CALD), defective suppressor cell activities were observed in eight cases (28%) for Ig synthesis and 16 cases (55%) for blast transformation study. The suppressor cell activities were decreased in two (22%) of nine cases with chronic persistent hepatitis and one (17%) of six cases with inactive cirrhosis for both Ig synthesis and blast transformation. In contrast, suppressor activities were inducible in all nine patients with acute viral hepatitis. The histocompatibility antigen DR4 was significantly increased in CALD patients, but there was no correlation between this antigen and suppressor cell activity. These findings suggest that altered lymphocyte suppressor cells in patients with CALD may contribute to the continuing liver cell injury in this disease.

Topics: Acute Disease; Adult; Chronic Disease; Concanavalin A; Hepatitis, Viral, Human; HLA Antigens; Humans; Immunoglobulins; Liver Diseases; Lymphocyte Activation; Middle Aged; Pokeweed Mitogens; T-Lymphocytes, Regulatory

Suppressor T cell function is decreased in patients with chronic active liver diseases (CALD). To account for the alterations, we examined the effect of sera of patients with various liver diseases on concanavalin A (Con A) induced suppressor T cell activity of normal individuals. The suppressor T cell activity was inhibited by heat-inactivated serum pretreatment in 13 of 27 cases of patients with CALD and in five of 11 cases of patients with acute viral hepatitis, whereas only two sera of 18 patients with other liver diseases affected suppressor cell activity. Using a 125I-C1q-binding test, a significant correlation (P less than 0.01) was detected between the degree of inhibition in the development of suppressor T cells and the level of circulating immune complexes in the sera of CALD patients. The blocking effect of patients' sera disappeared when the immune complexes were removed with polyethylene glycol. These data suggest that circulating immune complexes modulate cellular immunity in patients with CALD by influencing the suppressor T cell function.

Topics: Adult; Antigen-Antibody Complex; Chronic Disease; Complement Activating Enzymes; Complement C1q; Concanavalin A; Humans; Immunoglobulin G; Liver Diseases; Lymphocyte Activation; Middle Aged; Prednisone; T-Lymphocytes, Regulatory

Topics: Animals; Cell Adhesion; Chronic Disease; Concanavalin A; Creatinine; Immunity, Cellular; Lipopolysaccharides; Male; Mitogens; Phytohemagglutinins; Rats; Rats, Inbred WF; Spleen; Uremia

Topics: Adult; Cell Migration Inhibition; Chronic Disease; Concanavalin A; Hepatitis B; Humans; Leukocytes; Middle Aged

Tests on blastic transformation of peripheral blood lymphocytes after stimulation with nonspecific mitogens (PHA, Con A, PWM) were performed on 55 patients suffering from glomerulonephritis and 32 persons belonging to the control group. On the basis of results obtained, the patients with glomerulonephritis were divided into three groups. The first, comprised patients with acute proliferative glomerulonephritis in whom the values of blastic transformation after stimulation by three mitogens used did not differ from the control group. The second, comprised patients with chronic proliferative, membraneous-proliferative, and membraneous glomerulonephritis. In 1/3 of them, a decrease blastic response to one of three mitogens was observed which was most often connected with stimulation by Con A. The third group comprised patients in the active phase of submicroscopic glomerulonephritis and lupus nephritis showing the lowest values of blastic transformation. The estimation of mitogen-induced blastic transformation was repeated in 17 patients after several weeks of nonsteroid anti-inflammatory drug therapy. After the treatment, values of spontaneous blastic transformation decreased statistically significantly. The mean values of mitogen-stimulated blastic transformation were also lower after the treatment, but the difference was not statistically significant.

Topics: Acute Disease; Adolescent; Adult; Chronic Disease; Concanavalin A; Female; Glomerulonephritis; Humans; Lymphocyte Activation; Male; Middle Aged; Mitogens; Phytohemagglutinins; Pokeweed Mitogens

Forty-four human long-term survivors after marrow transplantation for aplastic anemia or hematologic malignancy were studied for the presence of circulating nonspecific suppressor cells. Twenty-two of the patients were healthy and 22 had mild to moderately severe chronic graft-vs-host disease (GVHD). Patient mononuclear cells (of donor origin) were tested for their ability to suppress the responses of lymphocytes obtained from the respective marrow donors to alloantigens in mixed leukocyte culture (MLC) and/or to concanavalin A (Con A). Tests were carried out between 199 and 2393 (median 376) days after transplantation. Cells from only 1 of 22 patients without chronic GVHD showed suppression of donor cell blastogeneis responses. In contrast, cells from 11 of 22 patients with chronic GVHD showed more than 30% suppression of donor cell responses in MLC and/or to Con A. The finding of suppressor cells was not related to the time of testing after grafting nor to immmunosuppressive therapy. Nonspecific suppressor activity was abrogated by irradiation with 1600 rads in vitro in five of six cases tested. Nonspecific suppressor cells may be one explanation for the severe combined immunodeficiency and the recurrent infectious complications characteristic of patients with chronic GVHD.

Topics: Bone Marrow Transplantation; Chronic Disease; Concanavalin A; Cyclophosphamide; Graft vs Host Reaction; Humans; Long-Term Care; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; T-Lymphocytes, Regulatory; Time Factors; Transplantation, Homologous

The activity of LIF after Con A stimulation was examined in patients with hemodialysis and chronic uremia. It was found that LIF activity is reduced in uremia compared with healthy controls. The absolute number of T lymphocytes was reduced as well as the number of active E rosettes. An inhibitory effect was found in vitro by isolated middle molecules from uremic serum and ultrafiltrate. The LIF production of normal lymphocytes and the number of active rosettes are significantly reduced by substances isolated from serum and ultrafiltrate with molecular weight of 1 000 to 1 500 Dalton. The authors think that these uremic middle molecules are responsible for the already known reducing of immune response by uremia. The uremic substances are dialysable.

Topics: Adult; Chronic Disease; Concanavalin A; Female; Humans; Leukocyte Migration-Inhibitory Factors; Lymphokines; Male; Renal Dialysis; Toxins, Biological; Uremia

Topics: Animals; Antibody Formation; Chronic Disease; Concanavalin A; Female; Hypersensitivity, Delayed; Intestinal Mucosa; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Mice, Nude; Nematode Infections; Nippostrongylus; Rats; Rats, Inbred Lew; Reagins; Time Factors

Lymphocytes were highly purified from synovial fluid and peripheral blood of 10 rheumatoid arthritis patients and assessed for responsiveness to PHA-P and Con-A. In all cases, both synovial and blood lymphocytes showed a marked reduction in response to these mitogens compared with normal blood lymphocytes. The factors responsible for this low T cell responsiveness are discussed.

Topics: Arthritis, Rheumatoid; Chronic Disease; Concanavalin A; Humans; Lymphocyte Activation; Phytohemagglutinins; Synovial Fluid

We have studied peripheral blood mononuclear cells obtained from 24 patients with acute or chronic active hepatitis to determine if there was an abnormality in concanavalin A-induced suppressor cell activity compared to control subjects. Suppressor cells were generated by preincubation of the mononuclear cells with a mitogenic concentration of concanavalin A (6 mug/ml) for 48 hr followed by treatment with mitomycin C and alpha-methyl mannoside. Suppressor cell activity was assessed in second cultures by inhibition of concanavalin A-stimulated blast transformation of fresh allogeneic lymphocytes. Concanavalin A-stimulated suppressor activity was not elicited in mononuclear cells from the majority of patients with chronic active hepatitis in contrast to patients with acute hepatitis or acute inflammatory diseases and controls (P < 0.001). This finding was demonstrable in chronic active hepatitis patients in remission and relapse, both on and off prednisone therapy, and varied considerably during the course of the disease. The extent of liver injury was not related to the measured suppressor cell activity. These studies suggest that in chronic active hepatitis, a disease in which the host immune response may be involved, there appears to be a defect in concanavalin A-stimulated suppressor cells.

Topics: Acute Disease; Adult; Aged; Aspartate Aminotransferases; Autoimmune Diseases; Chronic Disease; Concanavalin A; Female; Hepatitis; Humans; Immunosuppression Therapy; Lymphocyte Activation; Male; Middle Aged

Topics: Antigens; Chronic Disease; Concanavalin A; Culture Media; Dose-Response Relationship, Immunologic; Female; Humans; Immunity, Cellular; Immunosuppression Therapy; Lectins; Lymphocyte Activation; Ovum; Schistosoma mansoni; Schistosomiasis

Con A-Sepharose affinity chromatography may be used in the analysis and classification of immune complexes. Experiments with model immune complexes suggest that the degree of affinity of an immune complex for Con A-Sepharose is determined by the antigen rather than the IgG antibody of the complex. It is possible that partial characterization of unknown antigens linked to IgG in immune complexes may be achieved in many diseases. Preliminary explorations with selected human sera indicate that the IgG containing immune complexes in Burkitt's lymphoma and nasopharyngeal carcinoma have affinity for Con A-Sepharose. By contrast IgG containing immune complexes in chronic hepatitis B seem to lack affinity for Con A-Sepharose.

Topics: Antigen-Antibody Complex; Burkitt Lymphoma; Chromatography, Affinity; Chronic Disease; Concanavalin A; Hepatitis B; Humans; Immune Sera; Immunoglobulin G; Nasopharyngeal Neoplasms; Sepharose

Topics: alpha-Fetoproteins; Antibody Formation; Chronic Disease; Concanavalin A; Hepatitis; Humans; Immunity, Cellular; In Vitro Techniques; Lymphocyte Activation; T-Lymphocytes

Chronic murine schistosomiasis mansoni is associated with depressed cell-mediated immune responses to Schistosoma mansoni egg antigens. The present study has examined the possibility that factors develop during infection that are capable of altering the response of lymphocytes to stimuli other than specific schistosomal antigens. Egg production begins at 5 weeks, and 1 to 3 weeks later there is a moderate degree of unresponsiveness of lymph node and spleen cells to the mitogens concanavalin A and phytohemagglutinin. This was associated with an altered dose response curve to the mitogens similar to that observed in antigenic systems. Seven weeks after the initiation of antigenic stimulation (egg prodiction lymph node and spleen cells from chronically infected animals were profoundly unresponsive to all concentrations of concanavalin A and phytohemagglutinin tested. These investigations suggest that, in addition to possible blockade by serum antibody, other suppressive factors may be involved in the spontaneous modulation of immunopathology in chronic schistosomiasis. These are detectable 1 to 3 weeks after the onset of egg production and are prominent at 12 weeks. Such findings are consistent with, but do not prove, the existence of suppressor T cells in chronic schistosomiasis.

Topics: Animals; Antibody-Producing Cells; Chronic Disease; Concanavalin A; DNA; Female; Immunosuppression Therapy; Lectins; Lymph Nodes; Lymphocyte Activation; Mice; Schistosoma mansoni; Schistosomiasis; Spleen; T-Lymphocytes

Spleen cells from F1 mice undergoing chronic graft-vs-host (GVH) reaction, induced by injection of parental cells, were shown to be immunosuppressed since their in vitro responses to the mitogens concanavalin A (Con A) and bacterial lipopolysaccharide (LPS) were substantially lower than control animals. Serum, from mice undergoing GVH, when cultured in vitro with normal spleen cells was immunosuppressive. The proliferation response to Con A and allogeneic cells of normal syngeneic, allogeneic, and parental spleen cells was 90% suppressed when serum from mice undergoing chronic GVH was added in comparison to the addition of serum from untreated F1 mice. Similarly, the in vitro antibody response to a T-dependent antigen was impaired; however, the antibody response to a T-independent antigen was not impaired. These results indicate that T cell functions are more sensitive than are B cell functions to immunosuppressive factors in the serum of mice undergoing GVH.

Topics: Animals; Antibody Formation; Antilymphocyte Serum; B-Lymphocytes; Chronic Disease; Concanavalin A; Dose-Response Relationship, Drug; Graft vs Host Reaction; Hemolytic Plaque Technique; Immunosuppression Therapy; Lipopolysaccharides; Lymphocyte Culture Test, Mixed; Lymphocytes; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Inbred DBA; Spleen; T-Lymphocytes

Lymphocyte function in vitro was evaluated in patients with chronic active hepatitis and compared to normal controls. Circulating lymphocytes of patients were spontaneously cytotoxic to 51Cr-labeled human Chang liver cells and to suspensions of autologous liver cells obtained at the time of liver biopsy when tested at a lymphocyte target cell ratio of 200:1. Prednisone treatment of patients with chronic active hepatitis inhibited both spontaneous and concanavalin A-stimulated lymphocyte cytotoxicity to human Chang liver cells. Similarly, chronic prednisone administration substantially reduced lymphocyte cytotoxicity towards the patients' own liver cells in vitro, which correlated with a clinical, biochemical, and histological response to such therapy. Thus, patients with chronic hepatitis have circulating lymphocytes that are capable of causing destruction of their own liver cells in vitro. The beneficial effect of prednisone therapy in such patients may be related to this inhibition of lymphocyte cytotoxicity.

Topics: Cell Line; Cell Survival; Chronic Disease; Concanavalin A; Cytotoxicity Tests, Immunologic; Hepatitis; Humans; Liver; Lymphocytes; Prednisone

Peripheral lymphocytes from patients with hepatitis-B surface antigen (HBsAg)-positive and -negative acute hepatitis (AH), chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and normal controls were tested for in vitro cytotoxicity and blast transformation. Cytotoxicity was measured by chrominum (21Cr) release into the medium from 51Cr-labeled Chang liver cells after incubation for 6 h with peripheral lymphocytes at a lymphocyte target cell ratio of 200:1. Concomitant 72-h incubation studies were performed to assess thymus cell-dependent (T) lymphocyte function as measured by conccanavalin A (Con A)- stimulated incorporation of tritiated thymidine (blast transformation) and by cytotoxicity. It was found that (a) lymphocytes from patients with AH are cytotoxic to Chang liver cells compared to controls (P less than 0.001); (b) lymphocytes from patients with acute and chronic hepatitis are less cytotoxic when incubated with autologous and homologous HB2Ag-positive and -negative AH, CAH, and CPH are as cytotoxic as normal controls when stimulated with a nonspecific mitogen such as Con A; and (d) lymphocytes from patients with CAH while on prednisone therapy showed marked depression of cytotoxicity when stimulated with Con A. Thus these studies show that patients with AH have circulating T lymphocytes which are capable of causing the destruction of Chang liver cells. There is no defect in T-cell function as measured by Con A-stimulated cytotoxicity. There is a serum factor (s) in patients with acute and chronic hepatitis which inhibits spontaneous and induced lymphocyte cytotoxicity and blast transformation. Finally, prednisone treatment appears to inhibit lymphocyte cytotoxicity in patients with CAH.

Topics: Acute Disease; Adult; Antibodies, Viral; Antigens, Viral; Bilirubin; Cell Line; Chromium Radioisotopes; Chronic Disease; Concanavalin A; Cytotoxicity Tests, Immunologic; Female; Hepatitis B; Humans; Immune Sera; Immunity, Cellular; Jaundice; Liver; Lymphocyte Activation; Male; Middle Aged; Prednisone; T-Lymphocytes

The course of viral hepatitis is markedly influenced by the immunologic response to the infective agent. The immune defense of viral diseases is specially connected to an intact function of T lymphocytes. Investigation of T cell function during acute and chronic viral hepatitis showed an altered immune response, recognizable from the relative number of T lymphocytes, the affinity and ability of lymphocytes to be stimulated by phytohemagglutinin and the demonstration of in vivo activated lymphocytes. Although the interpretation of some of these findings is still difficult, the study of the various cellular immune reactions permits a better understanding of the pathogenesis and course of viral hepatitis.

Topics: Acute Disease; Autoantigens; B-Lymphocytes; Chronic Disease; Concanavalin A; Hepatitis A; Hepatitis B Antigens; Humans; Immunity, Cellular; Immunization; Lectins; Liver; Lymphocyte Activation; Macrophage Migration-Inhibitory Factors; T-Lymphocytes

Topics: Autoradiography; Blood; Chronic Disease; Concanavalin A; Culture Media; Female; Fluorescent Antibody Technique; Humans; Immunoglobulin A; Inclusion Bodies; Lectins; Leukemia, Lymphoid; Lymphocyte Activation; Lymphocytes; Microscopy, Electron; Middle Aged; Stimulation, Chemical; Thymidine; Tritium

Topics: Cells, Cultured; Chronic Disease; Concanavalin A; Humans; Lectins; Leukemia, Lymphoid; Lymphocyte Activation; Lymphocytes; Thymidine; Tritium