concanavalin-a and Immunologic-Deficiency-Syndromes

Topics: B-Lymphocytes; Cells, Cultured; Concanavalin A; Humans; Immune Tolerance; Immunologic Deficiency Syndromes; Infectious Mononucleosis; Lectins; Lymphocytes; Lymphokines; Receptors, Immunologic; Suppressor Factors, Immunologic; T-Lymphocytes; T-Lymphocytes, Regulatory

Topics: Animals; Concanavalin A; Dinitrochlorobenzene; Erythrocyte Transfusion; Female; Hemocyanins; Horses; Humans; Hypersensitivity, Delayed; Immunologic Deficiency Syndromes; Liver Transplantation; Lymphocyte Culture Test, Mixed; Male; Phytohemagglutinins; Rabbits; Sheep; Thymus Gland; Thymus Hormones

Immune abnormalities in psoriasis vulgaris are described. Anti-stratum corneum antibodies deposited with C3 have been found in patients with psoriasis. A lot of other immune abnormalities identified in psoriasis: increased serum IgG and IgA levels, lowered DNCB-sensitization, alteration in polymorphnuclear leukocytes (PMN) function, decreased number of T cells, lack of response to concanavalin A (ConA) and an increase in the polyclonal B cell activation. the authors believe that the immunoregulatory defect is due to the disorder of the skin.

Topics: Autoantibodies; B-Lymphocytes; Complement C3; Concanavalin A; Cornea; Dinitrochlorobenzene; Humans; Immunoglobulin A; Immunoglobulin G; Immunologic Deficiency Syndromes; Lymphocyte Activation; Neutrophils; Psoriasis; T-Lymphocytes

Topics: Agammaglobulinemia; Animals; Antigens; Autoimmune Diseases; Binding, Competitive; Cell Transformation, Neoplastic; Chickens; Concanavalin A; Dysgammaglobulinemia; Epitopes; Genes; Humans; Immune Tolerance; Immunity, Cellular; Immunoglobulin A; Immunoglobulin Allotypes; Immunoglobulin E; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Lymphokines; Mice; Mycoses; Rabbits; T-Lymphocytes

Measuring lymphocyte response to mitogens and antigens is a mainstay of screening for cellular immunodeficiency. Few reports analyze performance as a screening tool in diverse patient cohorts. We studied proliferation assays performed at Children's Hospital Boston from 1996 to 2003 using mitogens phytohemagglutinin (PHA), concanavalin A (CONA) and pokeweed mitogen, and antigens tetanus (TT) and diphtheria (DT) toxoids, and compared a subset of patients with T cell dysfunction with adult controls using receiver operating characteristic analysis. Results were correlated with clinical data. CONA was superior to PHA in identifying patients with immunodeficiency. TT was second best. Interpretation based on raw CPM, a stimulation index, or reference to simultaneous controls all performed equally. Combining data from multiple mitogens and/or antigens did not enhance performance. Proliferation testing is a useful component of screening for cellular immunodeficiency, but is not a sensitive predictor of cellular immune compromise or risk of opportunistic infection.

Topics: Adolescent; Adult; Child; Child, Preschool; Cohort Studies; Concanavalin A; Diphtheria Toxoid; Female; Humans; Immunologic Deficiency Syndromes; Infant, Newborn; Lymphocyte Activation; Male; Mitogens; Phytohemagglutinins; Pokeweed Mitogens; T-Lymphocytes; Tetanus Toxoid; Young Adult

Burn injury induces immune dysfunction and alters numerous physiological parameters. While clinical studies indicate that burn injury size profoundly impacts patient immune status, only limited experimental studies have systematically addressed its impact on immune functional parameters. In the present study, mice were subjected to burn injuries of varying sizes and splenic immune cells (splenocytes and macrophages) were isolated 7 days thereafter. Burn injury suppressed splenic T-cell proliferation in an injury size-dependent manner that correlated with the release of the immunosuppressive mediators PGE(2) and nitric oxide. In addition, a shift towards an immunosuppressive Th-2 cytokine profile and a hyperactive macrophage phenotype (increased release of inflammatory mediators) was observed post-injury, however, this effect was in part independent of burn size. Thus, unlike patient survival data, burn injury-induced changes in immune function do not necessarily correlate with the size of the injury.

Topics: Animals; Burns; Concanavalin A; Dinoprostone; Female; Immunologic Deficiency Syndromes; Lipopolysaccharides; Lymphocyte Activation; Lymphokines; Macrophage Activation; Mice; Mice, Inbred C57BL; Models, Animal; Nitric Oxide; Spleen; Th1 Cells; Th2 Cells

We examined T-cell proliferation in five patients with X-linked hyper-IgM syndrome (XHIM), using a panel of antigens and lectins. All patients had impaired antigen-induced proliferation, whereas their lectin responses were normal. Thus, in addition to severely depressed antibody responses, patients with XHIM have a defect in antigen-specific T-cell proliferation, which may explain their susceptibility to pathogens such as Pneumocystis carinii.

Topics: Antigens; Antigens, Fungal; Candida; CD40 Antigens; Concanavalin A; Cryptosporidiosis; Diphtheria Toxoid; Disease Susceptibility; Genetic Linkage; Humans; Hypergammaglobulinemia; Immunoglobulin M; Immunologic Deficiency Syndromes; Lectins; Ligands; Lymphocyte Activation; Male; Phytohemagglutinins; Pneumonia, Pneumocystis; Pokeweed Mitogens; T-Lymphocytes; Tetanus Toxoid; X Chromosome

The Fas (CD95)-transmitted cell death signal has been reported to involve a protein tyrosine phosphatase, SHP-1. We analyzed the role of SHP-1 in the Fas-dependent as well as the perforin-dependent pathways of CTL-mediated killing using target cells prepared from SHP-1-deficient motheaten mice. Con A blast targets prepared from both a motheaten mouse and a phenotype-normal littermate were equally sensitive to the cytolysis and DNA fragmentation induced by both perforin-deficient Fas-dependent CTL and Fas ligand-deficient perforin-positive CTL. Fas-induced DNA degradation detected by the terminal deoxynucleotide transferase reaction was also observed in the killing of motheaten thymocytes by a Fas-based CTL as well as by anti-Fas mAb. These data cast doubt on the involvement of SHP-1 in Fas-induced lymphoid cell death.

Topics: Animals; Apoptosis; Concanavalin A; Cytotoxicity, Immunologic; fas Receptor; Immunologic Deficiency Syndromes; Intracellular Signaling Peptides and Proteins; Lymphocyte Activation; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Mutant Strains; Perforin; Pore Forming Cytotoxic Proteins; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Protein Tyrosine Phosphatase, Non-Receptor Type 6; Protein Tyrosine Phosphatases; Rabbits; T-Lymphocytes, Cytotoxic

The authors investigated spontaneous and induced secretion of cytokins at different stages of generalized tuberculosis. In the development of infection there were inhibited IL-2 synthesis in response to ConA, emerging activity of PNO-alpha in response to the inductors in blood serum and culture of peritoneal macrophages, enhanced secretion of IL-6. Complete immunodeficiency was associated with cessation of IL-2 synthesis by splenocytes, elevated production of IL-6 by peritoneal macrophages, low concentrations of PNO-alpha in the serum and peritoneal macrophage cultures. In the treatment of M. bovis-infected mice with antibacterial drugs alone IL-6 secretion by peritoneal macrophages and PNO-alpha activity in the serum were increased. Immunocorrection resulted in marked activation of IL-2 production by splenocytes in response to ConA as well as enhanced synthesis of IL-6 in unstimulated cultures of peritoneal macrophages.

Topics: Adjuvants, Immunologic; Animals; Antitubercular Agents; Concanavalin A; Drug Evaluation, Preclinical; Drug Therapy, Combination; Immunity, Cellular; Immunologic Deficiency Syndromes; Interleukin-2; Interleukin-6; Isoniazid; Mice; Mycobacterium bovis; Rifampin; Thymus Hormones; Tuberculosis; Tumor Necrosis Factor-alpha

LEC rats are known to show a maturational arrest in the development of CD4+8+ to CD4+8- cells in the thymus. Despite the blockade of maturation of CD4+8-thymocytes, CD4+ T cells were observed in peripheral lymphoid organs, and these cells exhibit a defect in interleukin-2 (IL-2) production upon concanavalin A (Con A) stimulation. Although peripheral CD4+ cells in normal rat highly expressed CD45RC (CD45RChigh), the level of CD45RC expression was low (CD45RClow) in LEC rat peripheral CD4+ cells. However, CD4+ cells from both strains highly expressed CD45 when those cells were stained by pan-CD45 mAb, suggesting that LEC rat CD4+ cells are deficient in expression of the CD45RC isoform, but not of CD45 molecules. When backcross rats from (F344 x LEC)F1 x LEC were examined, the phenotype for CD45 expression pattern in CD4+ cells was clearly correlated with IL-2 production level in response to Con A stimulation. Thus, CD45RClow cells exhibit a defect in IL-2 production, while CD45RChigh cells show normal IL-2 production. Protein tyrosine phosphatase (PTPase) activity in the membrane fraction of LEC rat CD4+ cells was threefold higher than that of normal rat CD4+ cells. Con A stimulation led to an increase in tyrosine phosphorylation levels, especially 100- and 40-kDa proteins, in normal rat CD4+ cells. In LEC rat CD4+ cells, however, the level of tyrosine phosphorylation in those proteins were very low. These results suggest that an elevated CD45 PTPase activity is responsive for a defect in IL-2 production in LEC rat peripheral CD4+ T cells.

Topics: Animals; CD4-Positive T-Lymphocytes; Cell Differentiation; Concanavalin A; Enzyme Induction; Gene Expression Regulation; Immunologic Deficiency Syndromes; Interleukin-2; Isoenzymes; Leukocyte Common Antigens; Lymphocyte Activation; Lymphocyte Subsets; Phosphorylation; Protein Processing, Post-Translational; Protein Tyrosine Phosphatases; Rats; Rats, Inbred F344; Rats, Mutant Strains; RNA Splicing

To investigate the effect of bovine immunodeficiency virus (BIV) infection on the rabbit immune system, we studied the proliferative responses of peripheral blood lymphocytes (PBLs) of rabbits experimentally inoculated with BIV. All BIV127-inoculated rabbits seroconverted after 6 weeks and remained seropositive over a prolonged period of time. Assays for specific lymphocyte reactivity to concanavalin A (Con A) were performed monthly for over 1 year. One-hundred percent of infected rabbits developed abnormally low T cell responses, as measured by Con A stimulation. By 3 months postinoculation, the PBL response to Con A was diminished and remained depressed for 6 months. All animals were clinically asymptomatic within 14 months of BIV inoculation. By 15 and 16 months postinoculation, two of three infected rabbits exhibited recurrent lowering of the T cell responsiveness including a decrease in absolute PBL counts. One of these animals died unexpectedly. Our results further confirmed that a functional impairment of lymphocytes was induced early in the course of BIV infection, prior to clinical disease. These findings suggested that BIV infection may mimic asymptomatic infection of human immunodeficiency virus (HIV) and provided further evidence of the importance of BIV-induced disease in rabbits as a relevant model for the study of AIDS.

Topics: Animals; Antibodies, Viral; Cloning, Molecular; Concanavalin A; Immunodeficiency Virus, Bovine; Immunologic Deficiency Syndromes; Lentivirus Infections; Lymphocyte Activation; Lymphocytes; Male; Rabbits

We have assessed several age-sensitive indicators of immune status in young (i.e., 6 to 11-month-old) mice of a genetically heterogeneous population to see if these varied in parallel and to determine if one or more of the status indices predicted life span or cancer incidence. We report that the number of memory (i.e., CD44hi) T cells within the CD8 subset is correlated with number of memory cells in the CD4 population, and inversely correlated with the number of naive (i.e., CD45RBhi) CD4 cells at both 6 and 11 months of age, suggesting that the conversion of naive to memory cells may occur at similar rates in both T cell subsets. Mice that ranked high in the proportion of memory T cells (within the CD4 and CD8 pools) at 6 months of age tended to retain their ranking at 11 months, suggesting that the pace or extent of memory cell formation may be a consistent trait that distinguishes mice at least within a genetically heterogeneous population. Mice that at 6 months of age exhibited high levels of CD4 or CD8 memory T cells, low levels of naive CD4 cells, or low levels of T cells able to proliferate in response to Con A and IL-2 were found to be significantly more likely than their littermates to die within the first 18 months of life. Cases of follicular cell lymphoma, lymphocytic and lymphoblastic lymphoma, and hepatic hemangiosarcoma were seen within the group of mice dying at early ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Animals; Carrier Proteins; Cause of Death; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Concanavalin A; Female; Hyaluronan Receptors; Immunologic Deficiency Syndromes; Immunologic Memory; Interleukin-2; Longevity; Lymphocyte Activation; Lymphoma; Male; Mice; Mice, Inbred AKR; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Inbred Strains; Phenotype; Receptors, Cell Surface; Receptors, Lymphocyte Homing; T-Lymphocyte Subsets

Immunobiological activity of the polybacterial lysate Olimunostim (P. acnes, K. pneumoniae, S. aureus) was examined by investigating its effects on murine lymphocytes. When added to in vitro lymphocyte cultures, Olimunostim induced interleukin-2 (IL-2) biological activity (in a 2-d culture) and subsequently potentiated lymphocyte proliferation (on day 3); the latter effect was dependent on the presence of adherent cells. In vivo, significant enhancement of lymphocyte reactivity to T-mitogens and increase of CD4+ helper-inducer T lymphocytes were observed 3 d after a subcutaneous application of Olimunostim to mice with cellular immune deficiency. These results confirm the modulatory properties of Olimunostim towards lymphocytes both in vitro and in vivo, which may form a basis for its clinical application.

Topics: Adjuvants, Immunologic; Animals; Concanavalin A; Female; Immunity, Cellular; Immunologic Deficiency Syndromes; In Vitro Techniques; Interleukin-2; Klebsiella pneumoniae; Lymphocyte Activation; Lymphocytes; Mice; Mice, Inbred BALB C; Propionibacterium acnes; Staphylococcus aureus; T-Lymphocytes

The chemotactic, phagocytic, and candidacidal activities of peritoneal exudate macrophages from immunocompetent heterozygous (bg/+) and immunodeficient homozygous (bg/bg, bg/bg-nu/+, and bg/bg-nu/nu) beige mice were assessed. Overall, macrophages from all strains of mice tested not only were able to migrate into the peritoneal cavity in response to several eliciting agents but showed a comparable capacity to phagocytize fluorescein isothiocyanate-labeled, heat-killed Candida albicans. However, some populations of peritoneal exudate macrophages from homozygous beige mice (e.g., thioglycollate-elicited) and resident peritoneal macrophages from bg/bg mice incubated in vitro with supernatants from concanavalin A-stimulated splenocytes had poorer candidacidal activity than did control macrophages from bg/+mice. Interferon-gamma enhanced the in vitro candidacidal activity of macrophages from homozygous and heterozygous beige mice. As indicated by inhibitors, poor macrophage candidacidal activity seemed to correlate better with deficient nitric oxide--than with superoxide anion-mediated killing. These data suggest that impaired candidacidal activity of macrophages from homozygous beige mice may explain their enhanced susceptibility to candidiasis.

Topics: Analysis of Variance; Animals; Candida albicans; Cells, Cultured; Chemotaxis; Concanavalin A; Hot Temperature; Immunocompetence; Immunologic Deficiency Syndromes; Interferon-gamma; Lipopolysaccharides; Macrophages, Peritoneal; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mice, Nude; Mutation; Phagocytosis; Superoxide Dismutase; Thioglycolates

Patients with alcoholic hepatic cirrhosis have a higher predisposition to acquiring infections than healthy individuals, suggesting an alteration in the immune system. They also exhibit an important decrease in certain plasmatic constituents such as zinc, albumin, and transferrin which are involved in the normal immune response. The blastoid transformation of lymphocytes stimulated in vitro with phytohemagglutinin M and P in patients with alcoholic hepatic cirrhosis was studied and the results were correlated with the plasmatic constituents aforementioned. The rate of blastoid transformation was significantly lower (p < .001) in these patients when compared to the control group, but did not correlate directly with the concentration of zinc, albumin, transferrin or circulating globulins. Patients' plasma significantly inhibited the response of normal cells to stimulation with phytohemagglutinin and Concanavalin A; nevertheless, the blastoid transformation of lymphocytes in these patients was not restored to normal levels when incubated with control plasma.

Topics: Adult; Concanavalin A; DNA Replication; Female; Humans; Immunologic Deficiency Syndromes; Liver Cirrhosis, Alcoholic; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Serum Albumin; Transferrin; Zinc

The course of influenza and tuberculosis infections under the conditions of disturbances in the immune response of experimental animals has been studied. As revealed in the survival test, the induction of secondary T- and B-cell-mediated immunodeficiency in mice leads to an increase in the sensitivity of the body to influenza virus, especially in cases of T-cell-mediated immunodeficiency. The injection of BCG in combination with cyclophosphamide into mice induces tolerance to this antigen in the animals; this tolerance has a "split" character, i.e. it affects only T-cell-mediated, but not humoral immunity. The induction of T-cell-mediated immunodeficiency or tolerance to BCG in mice has been shown (in the survival test) to lead to the development of the sensitivity of the animals to experimental tuberculosis infection. B-cell-mediated immunodeficiency did not influence the animal survival rate.

Topics: Animals; B-Lymphocytes; BCG Vaccine; Concanavalin A; Cyclophosphamide; Immune Tolerance; Immunologic Deficiency Syndromes; Influenza A virus; Lipopolysaccharides; Male; Mice; Orthomyxoviridae Infections; Serratia marcescens; T-Lymphocytes; Tuberculosis

The presence of increased levels of suppressor T cells after thermal injury and their relevance remain controversial. It is unclear whether suppressor T cells are the cause or result of sepsis complicating thermal injury. Spleen cells from a standardized murine burn model and sham burn controls were studied and the relationship between the levels of suppressor cytotoxic T cells (CD8, Lyt-2+), helper T cells (CD4, L3T4+), response to concanavalin A (ConA) and to phytohemagglutinin (PHA) and interleukin-2 (IL-2) production was examined. Mortality following infection via cecal ligation and puncture (CLP) of matched controls was also studied. At day 7 postburn, mean ConA (70 +/- 12% of control) and PHA response (58% +/- 5.2% of controls) and IL-2 production (43% +/- 5.4%) were significantly less than sham burn values (100%; p less than 0.05). However, the mean percentage of cells staining with anti-Lyt-2 and anti-L3T4 (9.1 +/- 0.59 and 13.9 +/- 0.65) was similar to the mean percentage in sham burn animals (9.4 +/- 0.65 and 16.6 +/- 1.1). Furthermore, no significant differences were observed between burned mice and controls in helper (17.3% +/- 1.8% burn vs. 21.2% +/- 1.7% sham) or suppressor cell levels (7.8% +/- 1.2% burn vs. 8.6% +/- 0.7% sham) or helper-suppressor ratios on day 10 postburn. Mortality of 20 litter-matched controls subjected to CLP on day 10 postburn was 90%, which was significantly greater than the sham burn mortality of 20%.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Antibodies, Monoclonal; Biomarkers; Burns; CD4-CD8 Ratio; Concanavalin A; Disease Models, Animal; Evaluation Studies as Topic; Immunologic Deficiency Syndromes; Infections; Interleukin-2; Lymphocyte Activation; Male; Mice; Phenotype; Phytohemagglutinins; Predictive Value of Tests; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Discrete colonies of splenocytes were grown on filter paper discs in the presence of concanavalin A and interleukin 2. Phenotypic analysis of the colonies indicated that the majority expressed the Thy-1.2 marker and 72% of these co-expressed the CD3 molecule. Of the colonies 20%-25% were NK 1.1+ and they developed regardless of the presence of Con A in the culture medium, a property of the NK lineage. In addition, Thy-1.2+ colonies developed when splenocytes from scid mice, which lack mature T and B cells, were grown both in the presence and absence of concanavalin A. These results demonstrate that colonies of murine splenic T lymphocytes and NK cells could be successfully grown on filter paper discs and phenotypically characterized. With this colonies technique, it was possible to identify a novel subset of NK 1.1+ colonies that co-expresses CD3 and shares growth properties with T cell colonies.

Topics: Animals; Antigens, Differentiation, T-Lymphocyte; Antigens, Surface; CD3 Complex; Clone Cells; Concanavalin A; Filtration; Immunologic Deficiency Syndromes; Interleukin-2; Killer Cells, Natural; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Receptors, Antigen, T-Cell; Spleen; T-Lymphocytes; Thy-1 Antigens

Studies were conducted with two lines of chickens that were selected for high and low plasma protein concentrations in response to aflatoxin B1 (AFB1) exposure. The experiments were designed to determine genetic differences in the responses of T cells and thymocytes to the toxin. Chicks were orally administered AFB1 at a rate of 0, 100, or 500 micrograms/kg body weight up to 21 days of age. At 4 weeks of age, concanavalin A (Con A, 2.5 micrograms/mL) stimulated T-cell proliferation was similar for untreated chicks from the low line (LL) and the high line (HL). However, AFB1 reduced the responses of T cells with HL cells being more sensitive. In a second experiment, immature chickens were bled and peripheral blood lymphocytes were cultured with Con A and either 0, 3.125, 6.25, 12.5, or 25 micrograms/mL AFB1. T cells from LL had greater responses to Con A than those from HL, and LL T-cells were also more resistant to in vitro AFB1 exposure. Furthermore, thymocyte proliferation was greater for LL chicks; but when thymocytes were cultured with 25 micrograms/mL AFB1, 3H-thymidine incorporation was similarly reduced in both lines. Cell cycle analysis indicated that there were more LL thymocytes in S phase, and the percentages for both lines decreased with AFB1 treatment. Although there were no differences between the lines for percent G2/M cells, AFB1 treatment increased the percentages of thymocytes in G2/M. These studies showed that selection for plasma protein response also changed T-cell and thymocyte proliferative activity.

Topics: Aflatoxin B1; Animals; Blood Proteins; Cell Cycle; Cells, Cultured; Chickens; Concanavalin A; Ethanol; Immunity, Cellular; Immunity, Innate; Immunologic Deficiency Syndromes; Inactivation, Metabolic; Inbreeding; Lymphocyte Activation; Selection, Genetic; T-Lymphocytes

Topics: Administration, Inhalation; Animals; Atmosphere Exposure Chambers; Concanavalin A; Female; Hemolytic Plaque Technique; Immune System; Immunologic Deficiency Syndromes; Lipopolysaccharides; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred C57BL; Nitrites; T-Lymphocytes

This report focuses on cell-mediated immune functions in a patient with MHC class II deficiency. The patient described presented with a case of "classical" MHC class II deficiency (T and B cells within the normal range, normal lymphocyte proliferation in response to stimulation with mitogens, gene encoding for MHC class II present, no expression of MHC class II). The absence of MHC class II expression resulted in an incapability of the patient's antigen-presenting cells to function as accessory cells in the presentation of soluble protein antigens, while accessory functions required for the induction of alloantigen-induced lymphocyte proliferation or for the generation of cytotoxic T cells in response to an allostimulus were normal. The patient's T cells responded normally to alloantigenic stimulation and also had the capacity to develop antigen-specific cytotoxic functions. However, the T cells were completely naive with respect to activation by soluble protein antigens, even after presentation by accessory cells derived from the patient's healthy histoidentical brother. In this context it was interesting to note that the patient's CD4-positive cells showed a normal pattern of expression of the 4B4 marker, a marker generally present on memory T cells. These data make it tempting to speculate that in the absence of MHC class II, other cell surface structures may at least partially take over immune functions normally under the control of the MHC class II complex.

Topics: Antigens, CD; Bone Marrow Transplantation; Cell Division; Child; Concanavalin A; Cytotoxicity, Immunologic; Histocompatibility Antigens Class II; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Immunophenotyping; Immunotherapy; Interleukin-1; Leukocytes, Mononuclear; Male; Phytohemagglutinins

A fluorometric assay using Hoechst 33342 to measure DNA in cell culture has been applied to detect mitogenic stimulation of human lymphocytes. Mononuclear cells from the peripheral blood of healthy donors and of HIV infected patients were stimulated with mitogens (PHA and ConA, respectively) in serum-free culture medium (5 x 10(4) or 1 x 10(5) cells/well) and incubated with Hoechst 33342. Fluorescence intensities were read using an automated fluorescence reader against the dye solution as a blank. The stimulation index (fluorescence units of stimulated vs. unstimulated cell culture) was calculated and compared to the stimulation index obtained in the [3H]thymidine assay. A sensitivity of 94.6% and a specificity of 97.4% was observed for the fluorometric assay. The intra-assay variability (12.3-15.6%) and the interassay variability (9.6-21.8%) were calculated using 1 x 10(5) cells/culture for PHA stimulation. We recommend the inexpensive and rapid fluorometric Hoechst 33342 assay as an alternative procedure, for monitoring mitogen induced stimulation of human lymphocytes in the diagnosis of immunodeficiencies.

Topics: Adult; Benzimidazoles; Concanavalin A; DNA; Fluorometry; Humans; Immunologic Deficiency Syndromes; Lymphocyte Activation; Phytohemagglutinins

7,8-Disubstituted guanine ribonucleosides represent a class of B lymphocyte agonists that utilize a protein kinase C-independent signaling pathway. These compounds provide an alternate T helper signal for B cells and enhance antigen-specific humoral responses in the murine model and in an IL-2-dependent human model in vitro. They effectively restore high level immune responses in a variety of murine models of immunodeficiency both in vivo and in vitro. In this study we examined the potential of these compounds to improve antibody responses generated by cultured cells from patients with common variable immunodeficiency (CVI). The inability to mount normal humoral responses to antigen was confirmed in nine patients with diagnosed CVI (CVI: 37 +/- 16, normal 653 +/- 116 plaque-forming cells (PFC)/culture; P less than 0.001). In cultured lymphocytes from eight of the nine patients studied, a normal level or greater responses to nominal antigen could be elicited by antigen in the presence of the immunostimulatory nucleoside 7-methyl-8-oxoguanosine (7m8oGuo). The average response to antigen increased from 37 +/- 16 without nucleoside to 1733 +/- 488 PFC/culture in its presence (P less than 0.002). Restoration of specific immune responses was an antigen-dependent and nucleoside dose-dependent event. Signaling by 7m8oGuo rendered the response to antigen protein kinase C independent in cultures of cells from normal donors as well as from CVI patients. These data substantiate (i) that a non-C-kinase signaling pathway for antigen-dependent differentiation exists, (ii) that this pathway can function normally in B cells from patients with CVI when triggered appropriately, and (iii) that 7,8-disubstituted guanine ribonucleosides can convert a C-kinase-dependent signaling event to a C-kinase-independent signaling event. Substituted guanine ribonucleosides may have potential as immunotherapeutic agents for patients with CVI.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Adult; Alkaloids; Antibody Formation; Antigens, CD; Cell Division; Concanavalin A; Dose-Response Relationship, Drug; Female; Guanosine; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologic Deficiency Syndromes; Immunophenotyping; In Vitro Techniques; Isoquinolines; Lymphocytes; Male; Middle Aged; Piperazines; Pokeweed Mitogens; Protein Kinase C; Protein Kinase Inhibitors; Signal Transduction; Sphingosine; Staurosporine

RIIIS/J mice lack an autosomal dominant gene(s) that influences the magnitude of the antibody response to several polysaccharide antigens of bacterial origin. Low responsiveness is demonstrable whether polysaccharide is administered as a T-helper-cell-independent or -dependent antigen conjugated to an immunogenic carrier; however, RIIIS/J mice make good anti-hapten antibody responses to haptenated polysaccharides. The low antibody responses of RIIIS/J mice to type III pneumococcal polysaccharide do not appear to be the results of an imbalance in the activity of regulatory T lymphocytes. Compared with other strains of mice, RIIIS/J mice elicit low antibody responses to lipopolysaccharide (LPS). They do not develop a cyclic primary or secondary antibody response to Escherichia coli O113 LPS; the latter is not due to a lack of mitogenic response to E. coli O113 LPS. They also produce auto-anti-idiotypic antibody after being immunized with trinitrophenyl-Ficoll.

Topics: Animals; Antibody Formation; Antigens, Differentiation; Antigens, Ly; CD5 Antigens; Concanavalin A; Haptens; Immunologic Deficiency Syndromes; Immunologic Memory; Lipopolysaccharides; Lymphocyte Activation; Mice; Mice, Mutant Strains; Polysaccharides; Polysaccharides, Bacterial; Spleen

Mice with the autosomal recessive gene "wasted" (wst/wst) exhibit neurologic disorders, reduced mucosal immune responses, and abnormal DNA repair mechanisms. The wst/wst mouse has been proposed as a murine model for the human disorder ataxia telangiectasia. Experiments were designed to examine the sensitivity of T-cells from wasted mice to ionizing radiation. Results demonstrated that T-cell clones derived from wasted mice are more sensitive to the killing effects of gamma-rays than similar T-cell clones from control mice. Bulk thymocyte and splenic cell cultures demonstrated similar radiation sensitivity. Both thymic and splenic lymphocytes from wasted mice also expressed low proliferative responses to mitogenic stimulation with concanavalin A (Con A) that could not be attributed to an absence or reduction in T-cell number. However, following activation with Con A, cell cultures exhibited a marked decrease in the percentage of Thyl + cells in wasted mice, in contrast to cultures from control mice in which significant increases in Thyl + cells were observed. Furthermore, when cells were treated with gamma-rays in combination with Con A, Thyl + cells were decreased in control spleen and thymus, but were elevated in similarly treated wasted cultures. These changes were accompanied by an increase in cell volume in T-cells from wasted but not from control mice. These results describe the sensitivity of T-cells from wasted mice to ionizing radiation; in addition, they suggest that the wst/wst abnormality may be associated with cell cycle aberrancies.

Topics: Animals; Antigens, Surface; Concanavalin A; DNA; Gamma Rays; Immunologic Deficiency Syndromes; In Vitro Techniques; Lymphocyte Activation; Mice; Mice, Mutant Strains; RNA; Spleen; T-Lymphocytes; Thy-1 Antigens; Thymus Gland

The role of B cells in induction of phenotypic and functional abnormalities of T cells in a murine retrovirus-induced immunodeficiency syndrome, MAIDS, was evaluated in mice depleted of mature B cells from birth with anti-IgM antibodies (mu-suppressed) and infected at 4 wk of age. Multicolor FACS analyses of CD4+ T cell subsets showed that development of phenotypic abnormalities of these cells at 9 wk after infection was completely inhibited by mu-suppression. Furthermore, induction of impaired proliferative responses to Con A and alloantigens and CTL responses to alloantigens was fully blocked in antibody-treated animals. The extent of virus replication was comparable in spleens of untreated and mu-suppressed mice. Retroviral induction of T cell dysfunction in MAIDS is thus dependent on the presence of B cells, and high level virus expression in mice without B cells has little or no effect on T cell function.

Topics: Animals; B-Lymphocytes; CD4 Antigens; CD4-Positive T-Lymphocytes; Cells, Cultured; Concanavalin A; Enzyme-Linked Immunosorbent Assay; Immunoglobulin M; Immunologic Deficiency Syndromes; Leukemia Virus, Murine; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; T-Lymphocytes, Cytotoxic; Tumor Virus Infections

Murine bone marrow (BM) cells regulate a variety of immune responses via an endogenous natural suppressor (NS) activity. We demonstrate that BM-derived NS activity resides in an enriched fraction of large, low-density cells which have a high proliferative rate. Complement-dependent lysis of BM cells by antibody directed against markers of Veto and NK/LAK cells had no effect on NS activity. The BM of SCID mice and their littermate C.B-17 possessed normal NS activity. Conversely, the BM of NK-deficient C57 beige mice displayed reduced NS activity as compared to normal C57 black mice. Long-term BM cultures (LTBMC) generated in medium containing supernatants of Con A-stimulated (CAS) rat spleen cells resulted in the emergence of a population of cells which possessed NS activity greater than that of fresh BM cells. The LTBMC were also potent effectors of NK activity, as compared to fresh BM, which had little NK activity. Thus, while NS, NK/LAK, and Veto cells are all nonspecific effectors of immune suppression, the exact relationship between them is not clear.

Topics: Animals; Antibody Formation; Bone Marrow; Bone Marrow Cells; Cell Separation; Cells, Cultured; Concanavalin A; Immune Tolerance; Immunity, Cellular; Immunologic Deficiency Syndromes; In Vitro Techniques; Killer Cells, Lymphokine-Activated; Killer Cells, Natural; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Mice; Mice, Inbred Strains; Mice, Mutant Strains; Spleen; T-Lymphocytes, Regulatory

Splenocytes from mice of genotype scid/scid.bg/bg were tested in vitro to characterize the nature of the immunological deficit in these doubly mutant animals. The cells were unresponsive to the mitogens LPS and Con A and to alloantigens, as predicted for scid/scid genotype. Splenocytes from scid/scid.bg/bg lysed the NK cell-sensitive target cell line YAC at levels approximately 50% lower than those observed for scid/scid splenocytes. Splenocytes from SCID-beige mice failed to lyse the NK-resistant, LAK-sensitive cell line P815 but showed high levels of activity against the murine placental cell line Be6. Lytic activity was found in both nonadherent and plastic adherent cells and was eliminated by pretreatment of the effectors with anti-asialo-GM1 and complement. Incubation of 1 x 10(5) splenocytes with hrIL-2 failed to induce blastogenesis in scid/scid.bg/bg cells but produced a response in cultures of scid/scid or bg/bg spleen cells. However, blastogenesis and elevated levels of LAK-type killing were observed following incubation of higher numbers of scid/scid.bg/bg splenocytes in hrIL-2. Thus, doubly mutant scid/scid.bg/bg mice have reduced NK cell activity, in comparison to scid/scid mice, and appear to possess LAK-like effector cells and LAK cell precursors.

Topics: Animals; Cell Adhesion; Concanavalin A; Cytotoxicity, Immunologic; G(M1) Ganglioside; Genotype; Glycosphingolipids; Immunity, Cellular; Immunologic Deficiency Syndromes; Interleukin-2; Killer Cells, Lymphokine-Activated; Killer Cells, Natural; Lipopolysaccharides; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Mice; Mice, Mutant Strains; Recombinant Proteins; Spleen

To elucidate relationship between disease progress and immunologic alteration in feline immunodeficiency virus (FIV) infection, we classified naturally infected cats into clinical stage groups using the working criteria modified from those for human immunodeficiency virus (HIV) infection. Among the five distinct stages described for HIV infection, the three phases; asymptomatic carrier (AC), AIDS related complex (ARC), and acquired immunodeficiency syndrome (AIDS), were evaluated for concanavalin A (Con A)-induced lymphocyte blastogenic activities by using glucose consumption assay. There was a significant decrease of lymphocyte response in AC phase. The loss of response became marked as the disease progressed to ARC and AIDS, with an almost complete loss of mitogen response in AIDS phase. In addition to the loss of a lymphocyte function, AIDS in FIV infection was characterized by marked emaciation, anemia or pancytopenia, and postmortem evidences of opportunistic infections and lymphoid depletion.

Topics: Acquired Immunodeficiency Syndrome; AIDS-Related Complex; Animals; Carrier State; Cat Diseases; Cats; Concanavalin A; Female; Immunologic Deficiency Syndromes; Leukocyte Count; Lymphocyte Activation; Male; Retroviridae Infections

The blastformation tests using concanavalin A and pokeweed mitogen were carried out on peripheral blood lymphocytes obtained from cats infected with feline immunodeficiency virus (FIV). The infected cats included those showing multiple chronic disease, those with a single mild sign, and one with no clinical sign. The infected cats showed significantly lower mitogenic responses of peripheral lymphocytes to both mitogens and lower lymphocyte counts as compared to uninfected healthy cats. These immunologic alterations in the infected cats may be closely related to the development of immunodeficiency-like disorders associated with FIV.

Topics: Animals; Cat Diseases; Cats; Concanavalin A; Female; Immunologic Deficiency Syndromes; Lymphocyte Activation; Male; Pokeweed Mitogens; Retroviridae Infections

Indirect data supporting a preexisting immunologic impairment in patients with Hodgkin's disease (HD) have been presented in recent years. These immunologic defects are supposed to be related to genetic and/or environmental factors. In this study, 65 first-degree relatives and 12 spouses of 21 consecutive patients with HD were studied immunologically. Furthermore, seven twin pairs in which one partner had HD and four additional nonmatched healthy co-twins were also included in the study. A decreased lymphocyte DNA synthesis induced by Concanavalin A, a high spontaneous DNA synthesis, or a low CD4+/8+ ratio was found in 21 (32%) consanguineous, two (17%) nonconsanguineous relatives, and five (50%) healthy co-twins. The corresponding figures for the untreated patients with HD and the control series were 14 of 21 (65%) and 21 of 127 (16%), respectively. Total lymphocyte counts or lymphocyte subpopulations did not differ between HD relatives and controls. The increased frequency of blood lymphocyte defects among consanguineous first-degree relatives favors the existence of a genetically determined immune deficiency in at least a proportion of apparently healthy relatives of patients with HD. However, nongenetic factors such as age and environment may add to the defect.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Concanavalin A; DNA; Family Health; Female; Hodgkin Disease; Humans; Immunologic Deficiency Syndromes; Lymphocytes; Male; Middle Aged; Twins

An experimental model for testing antiviral agents against severe cytomegalovirus (CMV) infection in immunocompromised hosts was developed. The model consisted of cyclophosphamide (Cy) treatment of CMV-infected guinea pigs to simulate CMV infection in immunodeficient individuals. Of the 3 Cy regimens tested, a single 300 mg/kg dose administered one day after virus inoculation resulted in the most severe CMV infection considering mortality rates, mean day of death and loss of body weight. Evaluation of responses to both T and B cell mitogens suggested that the severe and lethal CMV infection resulted from the combined immunosuppressive effect of Cy and CMV. The nucleoside analog [9-(1-3-dihydroxy-2-propoxymethyl)guanine (DHPG) was used to assess the usefulness of the CMV-infected immunocompromised host model. DHPG (100 mg/kg/day for 8 days) prevented death but did not reduce virus infectivity titers in blood of Cy-treated, CMV-infected guinea pigs. This model of CMV infection in immunocompromised guinea pig is a relevant and convenient experimental tool for the assessment of candidate anti-CMV agents under well-defined experimental conditions, such as appropriate CMV inoculum and Cy regimen.

Topics: Acute Disease; Animals; Antiviral Agents; Cells, Cultured; Concanavalin A; Cyclophosphamide; Cytomegalovirus Infections; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Ganciclovir; Guinea Pigs; Immunologic Deficiency Syndromes; Lymphocyte Activation

This article describes the construction and establishment of a double congenic nude, beige C57BL/6 (B6 nu, bg) mouse strain. The mice do not show higher fragility than C57BL/6 nude mice and the double congenic strain can be maintained under conventional mouse housing conditions. Although the B6 nu, bg display a very low natural killer activity which cannot be enhanced by an interferon inducer (poly(I-C], they lack responsiveness to a T cell mitogen (concanavalin A); and they also show extremely low responsiveness to a B cell mitogen (0128: B12 Escherichia coli lipopolysaccharide) probably as a result of combined effects of the beige and nude genes in the C57BL/6 genetic context.

Topics: Animals; B-Lymphocytes; Concanavalin A; Immunologic Deficiency Syndromes; Killer Cells, Natural; Lipopolysaccharides; Lymphocyte Activation; Mice; Mice, Mutant Strains; Mice, Nude; Pedigree; Poly I-C; Spleen; T-Lymphocytes

Topics: Animals; Concanavalin A; Graft vs Host Reaction; Hemolytic Plaque Technique; Immunologic Deficiency Syndromes; Intestine, Small; Lymph Nodes; Lymphocyte Activation; Male; Organ Size; Rats; Rats, Inbred Lew; Spleen; Thymus Gland

Cellular and genetic analyses of interleukin-2 (IL-2) production and IL-2 receptor (IL-2R) expression were examined in a immunodeficient patient and his family members. Mononuclear cells (MNC) of the patient showed no proliferative response (stimulation index, less than 2) to T-cell mitogens (PHA and Con A) and were defective in IL-2 production and IL-2R expression (less than 1%), whereas productions of other lymphokines (B-cell differentiation factor and IFN-gamma) were not impaired significantly. His brother died of the same disease and his father also lacked in proliferative response and IL-2 production by PHA stimulation. In Southern blot analyses using DNA probes of IL-2 and IL-2R, patterns of the patient were the same as those of healthy volunteers, whereas the transcription of DNA coding for IL-2R to mRNA was lacking in the patient. These results suggest that inheritant defects of IL-2 production and IL-2R expression reside in this family and the defects are not linked to DNAs coding for IL-2 and IL-2R but to a transcriptional deficiency.

Topics: Concanavalin A; Gene Expression Regulation; Humans; Immunologic Deficiency Syndromes; Interleukin-2; Leukocytes, Mononuclear; Lymphocyte Activation; Lymphokines; Male; Phytohemagglutinins; Receptors, Immunologic; Receptors, Interleukin-2; T-Lymphocytes

C.B-17 scid (severe combined immunodeficiency disease) mice were used to evaluate the relationship of dendritic Thy-1+ epidermal cells (EC) to T lymphocytes (deficient in scid) and to NK cells (replete in scid). Epidermis from scid mice was deficient in dendritic Thy-1+ cells as determined by immunofluorescent staining of epidermal whole mounts. Similarly, epidermal cell suspensions from scid mice failed to proliferate in response to Con A, as compared with epidermal cell suspensions from C.B-17 control mice. Transplantation of normal bone marrow into scid mice reconstituted morphologically identifiable dendritic Thy-1+ EC in whole mounts, as well as Con A responsiveness of EC suspensions, thus indicating that the deficiency in dendritic Thy-1+ EC in scid mice is at the precursor level. These studies demonstrate that Thy-1+ EC are more closely related to T lymphocytes than to NK cells.

Topics: Animals; Antigens, Surface; Bone Marrow Transplantation; Cell Differentiation; Concanavalin A; Dendritic Cells; Epidermis; Immunologic Deficiency Syndromes; Lymphocyte Activation; Mice; Mice, Mutant Strains; T-Lymphocytes; Thy-1 Antigens

Lymphocytes from 22 patients with established malignancy were stimulated with concanavalin A (Con A), and supernatants were tested for T-lymphocyte chemotactic factor (LCF). LCF activity was measured using a leading front chemotaxis assay with normal human T cells as responders. Fifteen of the 22 patients tested produced LCF at a level of less than 2 standard deviation below the mean of control cells. In 10 patients where mononuclear cells were stimulated with Con A for 24, 48, and 72 hr, LCF activity was significantly reduced at all three time points averaging 38, 14, and 43% of control levels, respectively. In 13 of the 31 patients, patient T-cell migration in response to casein was measured and compared to the production of LCF by mononuclear cells from these same patients. A significant correlation was observed indicating that both the response of T cells to a migration stimulus, and the production of T-cell-derived LCF was comparably suppressed. The reduction in LCF production by mononuclear cells from patients with established malignancy was not reversed by the addition of indomethacin to the culture system during Con A stimulation indicating that inhibition was not mediated by excessive prostaglandin production. The addition of patient mononuclear cells or T cells to normal mononuclear cells resulted in the inhibition of normal cell LCF by patient mononuclear cells or T cells. This could not be attributed to the production of a lymphocyte chemotactic inhibitor by patient cells, but appeared instead to be due to the direct inhibition of normal cell LCF synthesis or release by patient mononuclear cells or T cells. Separation of patient T cells into Leu 2 suppressor/cytotoxic or Leu 3 helper/inducer T cells showed that the inhibitory activity was associated with the Leu-2 T-cell subset. Heterologous normal Leu 2 T cells did not suppress normal mononuclear cell LCF production suggesting that patient Leu 2 T cells were functionally activated as compared to normal Leu 2 cells. The decreased production of LCF coupled with a depressed T-cell migratory activity in patients with established malignancy may in part be responsible for suppressed cellular immune reactions in these patients and possibly the impairment of tumor rejection.

Topics: Adolescent; Adult; Aged; Cell Separation; Chemotactic Factors; Chemotaxis, Leukocyte; Concanavalin A; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Lymphocyte Activation; Middle Aged; Neoplasms; T-Lymphocytes; T-Lymphocytes, Regulatory

Intraperitoneal administration of group A streptococcal cell walls to Lewis rats induces a chronic arthritis, whereas the Fischer strain is resistant to the development of the lesion. Spleen cells from cell wall-treated rats (Lewis and Fischer) are deficient in the synthesis of IL-2. Using an mAb directed against the rat IL-2-R, the present studies indicate that the expression of IL-2-R on spleens of cell wall-treated rats is normal. However, the addition of exogenous IL-2 to spleen cells cultured with Con A does not stimulate the mitogenic response.

Topics: Animals; Arthritis; Cell Wall; Concanavalin A; Female; Immunologic Deficiency Syndromes; Interleukin-2; Lymphocyte Activation; Rats; Rats, Inbred F344; Rats, Inbred Lew; Receptors, Immunologic; Receptors, Interleukin-2; Spleen; Streptococcus pyogenes

Recently, a colony of Lewis rats has been described which is resistant to experimental allergic encephalomyelitis (EAE). These rats, termed Le-R, are still histocompatible with other Lewis rats. The genetic defect which results in EAE-resistance was shown not to be linked to the RT1.B (Ir) region of the MHC. Myelin basic protein (BP)-sensitization of Le-R rats induces cells capable of mounting a proliferative response to BP in culture but incapable of transferring EAE after culture with BP. The present study demonstrates that the latter deficiency can be overcome either by incorporating lipopolysaccharide (LPS) in the BP-culture medium or by simultaneous transfer of LPS-activated antigen-nonspecific spleen cells with the BP-sensitized cells. The BP-sensitized Le-R cells fail to transfer EAE due to their inability to initiate lesions in the CNS. LPS, working through an antigen-nonspecific cell or cell products, can correct the defect in the Le-R cells such that the antigen-specific cells become capable of initiating CNS lesions which lead to development of clinical EAE.

Topics: Animals; Concanavalin A; Encephalomyelitis, Autoimmune, Experimental; Epitopes; Guinea Pigs; Immunity, Innate; Immunization, Passive; Immunologic Deficiency Syndromes; Lymphocyte Activation; Myelin Basic Protein; Rats; Rats, Inbred Lew; Rats, Inbred Strains

Immunologic surface markers, 5'-nucleotidase activity, and in vitro cell functions were determined on peripheral blood mononuclear cells from 20 patients with primary humoral immunodeficiencies. Imbalances of T-cell subsets were a frequent finding and often associated with a deficiency of helper T lymphocytes, predominantly in common variable immunodeficiency. The magnitude of the blastogenic response to mitogens was subnormal in the majority of the samples and showed no correlations to the proportions of helper, suppressor T cells or monocytes in the cultures. Moderate to marked suppression of the pokeweed mitogen-driven allogenic B-cell maturation was mostly mediated by T lymphocytes but modified by monocytes in some patients. In identical twins, T lymphocytes selectively suppressed IgA production. Both in sex-linked agammaglobulinemia and common variable immunodeficiency the activity of 5'-nucleotidase was significantly lower than in controls. This deficiency was mediated by T lymphocytes and showed no correlations to imbalances of T-cell subpopulations or to alterations of lymphocyte functions.

Topics: 5'-Nucleotidase; Adolescent; Adult; B-Lymphocytes; Child; Concanavalin A; Humans; Immunoglobulin G; Immunoglobulin M; Immunologic Deficiency Syndromes; Lymphocyte Activation; Male; Monocytes; Nucleotidases; Phytohemagglutinins; Pokeweed Mitogens; Receptors, Antigen, B-Cell; T-Lymphocytes; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory

Immune deficiency, as defined by significant decreases in lymphocyte Con A and allo-reactivity and in natural killer (NK) function, was induced in normal adult mice by i.p. injections of combinations of allogeneic testicular germ cells and splenic leukocytes over 3 wk. This immune deficiency was evident at 8 wk after initial injection, and profound by 12 wk. Neither leukocytes nor testicular cells, given alone, were able to induce similar immune deficiency. These findings suggest the possibility that allogeneic germ cells and leukocytes of semen, on repeated administration, may induce immune deficiency and may act as co-factors to viral agents in the development of clinical AIDS in humans.

Topics: Animals; Concanavalin A; Cytotoxicity, Immunologic; H-2 Antigens; Immunologic Deficiency Syndromes; Killer Cells, Natural; Leukocyte Transfusion; Leukocytes; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Mice; Mice, Inbred AKR; Mice, Inbred C57BL; Spermatozoa

Equine lymphocytes incubated with Con A and isolated on discontinuous BSA density gradients suppressed mixed lymphocyte reactions in a cell dose- and Con A dose-dependent manner. Suppressor lymphocytes were radiosensitive, even after the initial Con A incubation phase was completed. Suppressor activity was consistently demonstrated using peripheral blood mononuclear leukocytes from normal horses, but was absent in thymus cells and variably present in lymph node cells. Suppressor lymphocytes were present in horses with selective IgM deficiency, and within neoplastic lymph nodes from a horse with lymphosarcoma and concomitant IgM deficiency. Suppressor cells were not detected in 5 of 6 horses with severe combined immunodeficiency.

Topics: Animals; Cell Separation; Concanavalin A; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Dysgammaglobulinemia; Horse Diseases; Horses; Humans; Immunoglobulin M; Immunologic Deficiency Syndromes; Inosine Pranobex; Lymphocyte Culture Test, Mixed; Lymphoma, Non-Hodgkin; T-Lymphocytes, Regulatory

Peripheral blood mononuclear cells (PBMC) from 40 patients with a variety of primary immunodeficiency diseases were examined for concanavalin A (Con A) inducible suppressor activity against proliferative response of autologous and allogeneic PBMC to phytohaemagglutinin (PHA). 45% (12/27) of the patients with common variable immunodeficiency and 86% (6/7) of the patients with selective IgA deficiency demonstrated lack of Con A-induced suppressor activity against proliferative response of autologous/allogeneic PBMC. 2 of 4 patients with X-linked agammaglobulin and both patients, each with Wiskott-Aldrich syndrome and ataxia-telangiectasia, also showed deficient suppressor function. This study demonstrates a deficiency of Con A-inducible suppressor-cell activity in a variety of immunodeficiency diseases. Possible underlying mechanisms for this functional defects are discussed.

Topics: Adolescent; Adult; Child; Concanavalin A; Humans; Immunologic Deficiency Syndromes; Middle Aged; T-Lymphocytes, Regulatory

T-Lymphocyte number and functions are often reduced, while B-lymphocyte function is often increased in patients with autoimmune disorders. To study the mechanisms responsible for these T-cell malfunctions in autoimmunity we adapted the murine experimental autoimmune myasthenia gravis (EAMG) model. Splenocytes from C57BL/6 mice immunized with acetylcholine receptors (AChR) in complete Freund's adjuvant (CFA) produced approximately half the amount of concanavalin A (Con A)-induced interleukin 2 (IL-2) as did splenocytes of CFA-inoculated controls. Further, AChR plus CFA-immunized splenocytes showed a marked reduction in T-cell proliferative responses induced by Con A or phytohemagglutinin when compared with CFA-inoculated controls. By contrast, lipopolysaccharide-induced B-cell function is preserved. Deficient Con A splenic T-cell response is seen early after secondary inoculation with CFA or AChR in CFA. T-Cell recovery occurs in CFA-inoculated mice but not in AChR plus CFA-inoculated mice. Defective Con A splenic T-cell response seen early after secondary immunization with CFA or AChR in CFA is due to the presence of a defective splenic adherent cell population. Moreover, defective Con A splenic T-cell response seen after established autoimmunity to AChR in EAMG is also due to the presence of a defective splenic adherent cell population.

Topics: Animals; Autoimmune Diseases; Cell Adhesion; Concanavalin A; Female; Freund's Adjuvant; Immunity, Cellular; Immunization, Secondary; Immunologic Deficiency Syndromes; Interleukin-2; Kinetics; Lymphocyte Activation; Mice; Myasthenia Gravis; Receptors, Cholinergic; Spleen; T-Lymphocytes; T-Lymphocytes, Regulatory

The results of a study on the induction of IFN-alpha, IFN-beta, and IFN-gamma in normal and SCID foals showed a deficiency of IFN-gamma but not IFN-beta in SCID foals. The ability of SCID mononuclear cells to produce IFN-alpha in response to poly I:C but not to NDV may indicate a partial deficiency of IFN-alpha in SCID foals. The deficiency of IFN-gamma and presence of IFN-beta in SCID foals supports the classification of IFN-gamma and IFN-beta as immune and nonimmune interferons, respectively. Furthermore, the deficiency of IFN-gamma in SCID foals may in part explain the high susceptibility to infections observed in SCID foals.

Topics: Animals; Cells, Cultured; Concanavalin A; Female; Horse Diseases; Horses; Immunologic Deficiency Syndromes; Interferons; Monocytes

The immunoregulatory system has recently been shown to require prostaglandins (PG) for its activation in man. We report here an impairment of immunoregulatory function, due to defective PGE monocytic production, in a 12-month-old boy with multiple carboxylase deficiency (MCD). The abnormal immune-response was corrected in vitro by adding PGE to the medium. Moreover, PGE deficiency and immunoregulatory dysfunction responded to biotin administration in vivo. It is suggested that the PGE deficiency in MCD could result from an impaired activity of a biotin enzyme, acetyl CoA carboxylase, since the product of this enzyme reaction, malonyl CoA, is required for prostaglandin synthesis.

Topics: Biotin; Carboxy-Lyases; Concanavalin A; Dinoprostone; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Infant; Lymphocyte Activation; Male; Monocytes; Prostaglandins E; T-Lymphocytes, Regulatory

We investigated the immune function of a patient with anergy and acquired hypogammaglobulinemia. Despite normal numbers of B cells and T4+ inducer and T5+ suppressor T cells, this patient's lymphocytes did not produce immunoglobulin, proliferate in response to soluble antigens, or generate helper factors in vitro. In addition, her T4+ T cells did not express la molecules after stimulation by soluble antigen. In mixing experiments, her T cells did not induce immunoglobulin secretion by B cells from a normal, HLA-D-identical sibling; this failure was not due to excessive suppression, since the patient's T cells did not abrogate immunoglobulin production by the normal sibling's T and B cells. Moreover, the patient's B cells secreted immunoglobulin in the presence of the sibling's T4+ cells. In contrast to the deficient inducer cells, the patient's T5+ T cells were capable of expressing suppressor-cell functions. These results indicate that immunodeficiency may occur because of a selective loss of T4+ inducer function.

Topics: Agammaglobulinemia; Antibody Formation; Child; Concanavalin A; Female; Histocompatibility Antigens Class II; Humans; Immunologic Deficiency Syndromes; Isoantigens; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; T-Lymphocytes

We have investigated the induction of antibody responses to erythrocyte (RBC)-bound antigens in the (CBA/N x B10)F1 mouse. Male B cells, which express the CBA/N defect, were shown to be unresponsive to RBC antigens when the delivered T cell helper activity was solely nonspecific. Thus we demonstrated that defective B cells did not respond to concanavalin A supernatants or bystander helper activity, in spite of the fact that CBA/N-defective mice could produce these T cell activities. The defective B cell did not respond to RBC-bound antigen in the presence of RBC-primed T cells, although the magnitude of this response was usually twofold less than normal controls. The insensitivity of CBA/N defective B cells to nonspecific T cell helper activities seemed to involve at least the inability of RBC antigens to activate defective B cells in the absence of antigen-specific T cell help.

Topics: Animals; Antigens; B-Lymphocytes; Concanavalin A; Erythrocytes; Female; Horses; Immunologic Deficiency Syndromes; Male; Mice; Mice, Inbred CBA; Perissodactyla; Sex Chromosome Aberrations; Sheep; T-Lymphocytes; X Chromosome

Darier's disease (Keratosis follicularis) a dominantly inherited keratinizing disorder of the skin, is associated with the development of severe, progressive viral and bacterial skin infections. We investigated the possibility that an inadequacy of the immune system might be responsible for this tendency. Seven of our 8 patients with Darier's disease showed complete anergy to common skin test antigens and their peripheral blood lymphocytes failed to produce the lymphokine, leukocyte inhibitory factor (LIF) in vitro when stimulated with the same antigens. One Darier's patient and 6 controls showed positivity to at least one skin test antigen and produced lymphokine in vitro to the appropriate antigen. All patients had normal leukocyte and differential counts and normal numbers of circulating T and B cells. All 8 patients with Darier's disease demonstrated no proliferative response to optimal doses of the T cell mitogen Con A while showing normal responses to the T cell stimulant PHA and the T cell dependent B cell stimulant PWM. This previously unreported finding suggests a subtle abnormality of T cells in Darier's and might be a marker for these patients. Serum from 2 patients with Darier's disease did not suppress the in vitro immunologic activity of lymphocytes from normals. Finally, 13-Cis-retinoic acid in dosages adequate to clear their skin disease did not alter the in vivo or in vitro immunologic functions in 3 Darier's patients, suggesting that the immune dysfunction is not a secondary phenomenon.

Topics: Adult; Aged; Concanavalin A; Darier Disease; Female; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; In Vitro Techniques; Isotretinoin; Leukocyte Migration-Inhibitory Factors; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Skin Tests; Tretinoin

Aged mice of the CBA/Ca strain, 15 months of age, and A/J mice, 17 months of age, exhibited impaired lymphoblastogenic response to concanavalin A but not to lipopolysaccharide. This defective cellular responsiveness was not accompanied by decreased antibody response to protein antigen or decreased ability to develop delayed hypersensitivity to picryl chloride. An increased susceptibility to influenza virus infection given intranasally was noted in the aged mice as compared with young animals. Such virus infection also impaired the lymphoblastogenic response to mitogens. Surprisingly, the virus infection in aged animals was less lethal after a subsequent infection with a small inoculum of Listeria bacteria.

Topics: Administration, Intranasal; Aging; Animals; Antibody-Producing Cells; Concanavalin A; Cytotoxicity, Immunologic; Female; Immunologic Deficiency Syndromes; Injections, Intraperitoneal; Listeriosis; Lymphocyte Activation; Mice; Mice, Inbred A; Mice, Inbred CBA; Orthomyxoviridae Infections

Topics: Animals; Concanavalin A; Erythrocytes; Humans; Immunologic Deficiency Syndromes; Lithium; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Monocytes; Phagocytosis; Phytohemagglutinins; Rosette Formation; Sheep; T-Lymphocytes, Regulatory

Topics: Agammaglobulinemia; Animals; Autoimmune Diseases; Chickens; Concanavalin A; Humans; Immunologic Deficiency Syndromes; Lymphocyte Cooperation; Macrophages; Mice; Mycoses; Neoplasms; Prostaglandins; T-Lymphocytes; T-Lymphocytes, Regulatory

The staphylococcal cell wall component protein A (SpA) and formalinized, Cowan I strain Staphylococcal organisms (STA) were compared with the lectins phytohemagglutinin, concanavalin A, and pokeweed mitogen for their ability to trigger proliferation of normal human lymphocytes, lymphocyte subpopulations, and cells from patients with primary immune deficiency diseases. SpA was found to be a potent T cell mitogen, very similar to the other lectins tested. It failed to stimulate purified non-T cells and peripheral blood lymphocytes from patients with different forms of severe combined immunodeficiency disease (SCID). STA, treated to prevent the leakage of soluble SpA during culture, exclusively stimulated non-T cells: the responding cell population was characterized to be E-rosette negative but positive for C3 receptors, surface Ia, a receptor for STA itself, and likely carried surface immunoglobulin. Normal responses to STA were found in patients with the adenosine deaminase-positive form of SCID. In 18 patients with humoral immune deficiency syndromes, the presence of STA responses was correlated with the presence of circulating, surface immunoglobulin-bearing cells. A commercial STA preparation was rendered B cell specific after reformalinization, a procedure that eliminated the shedding of soluble SpA under culture conditions.

Topics: Animals; B-Lymphocytes; Complement C3; Concanavalin A; Humans; Immunologic Deficiency Syndromes; Lymphocyte Activation; Mitogens; Palatine Tonsil; Phytohemagglutinins; Pokeweed Mitogens; Rosette Formation; Staphylococcal Protein A; Staphylococcus; T-Lymphocytes; Thymus Gland

We have analyzed the assembly of microtubules and the distribution of concanavalin A(Con A)-receptor complexes in the same populations of human peripheral blood T and B lymphocytes. We hoped to resolve the prolonged controversy over the relationship of microtubules to Con A cap formation in lymphocytes and to explain the abnormally high spontaneous and colchicine-induced Con A capping that was observed recently in lymphocytes from a patient with an inherited form of severe combined immunodeficiency disease (SCID) characterized by total immunologic dysfunction despite normal numbers and distribution of T and B cells. The data establish that (i) microtubule disassembly is correlated with enhanced Con A cap formation on normal human lymphocytes; (ii) T and B cells differ significantly from each other and from circulating polymorphonuclear leukocytes with respect to their capping responses after exposure to colchicine; and (iii) there is an abnormal relationship of microtubule assembly to surface topography in the functionally defective SCID cells.

Topics: B-Lymphocytes; Colchicine; Concanavalin A; Fluoresceins; Humans; Immunologic Capping; Immunologic Deficiency Syndromes; Lymphocytes; Microscopy, Fluorescence; Microtubules; Morphogenesis; Neutrophils; Receptors, Concanavalin A; T-Lymphocytes

Topics: B-Lymphocytes; Concanavalin A; Female; Humans; Immunoglobulin G; Immunologic Deficiency Syndromes; Infant; Leukocyte Count; Lymphocytes; Phytohemagglutinins; Pokeweed Mitogens; Receptors, Antigen, B-Cell; Rosette Formation; Skin Tests; Thymus Gland

Cultures of lymphocytes from a patient with a suppressed immune-system were set up, and a low response was seen after treatment with mitogenic substances such as PHA and ConA. Other lymphocyte cultures from the same patient were treated with Levamisole, and after this it was noted that the percentage of T-cell rosettes with sheep erythrocytes was increased.

Topics: Animals; Cells, Cultured; Concanavalin A; Humans; Immunologic Deficiency Syndromes; Levamisole; Lymphocytes; Phytohemagglutinins; Rosette Formation; T-Lymphocytes

A micromethod for the study of lymphocyte stimulation using small volumes of blood obtained by heel skin or fingertip puncture is described. Heel skin puncture samples from 15 full term newborns and venous blood samples from 6 newborns gave very similar results. A study of paired venous blood and fingertip puncture samples from 5 normal adults and 2 children with severe combined immunodeficiency (SCID) showed no significant differences between lymphocyte responses of samples taken from these sites. The responses of adults were significantly lower than those of the full term newborns, while the responses of the SCID patients were markedly depressed. Lymphocyte stimulation studies using blood samples obtained by heel skin or finger puncture provide a useful method for detection of defects in cellular immunity in young infants.

Topics: Cells, Cultured; Concanavalin A; Foot; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Infant, Newborn; Lymphocyte Activation; Phytohemagglutinins; Pokeweed Mitogens; Skin; Veins

The plasma immunoglobulins of patients with severe combined immunodeficiency were studied by immunoelectrophoresis and, following isolation by affinity chromatography, by SDS-polyacrylamide gel electrophoresis. Immunoglobulins in plasma from the eight patients studied were immunoelectrophoretically abnormal. Although certain of the immunoglobulins in plasma from five patients could not be identified antigenically, all possessed two mu determinant-bearing proteins with abnormally fast electrophoretic mobilities. Molecular analysis of immunoglobulins of three of these patients revealed two mu heavy chains of abnormally low molecular weight which lacked the ability to polymerize into the pentameric structure of IgM. The failure of concanavalin A to precipitate these molecules suggests that they lack the carbohydrate moiety of normal IgM. Using these techniques, we documented the acquisition of normal IgM synthesis by a patient grafted with maternal leukocytes and the partial immunologic development of a child maintained under gnotobiotic conditions. In the latter patient, between the age of 1 and 4 years, an abnormal mu component disappeared from plasma and normal IgM appeared.

Topics: Chemical Precipitation; Child, Preschool; Chromatography, Affinity; Concanavalin A; Electrophoresis, Polyacrylamide Gel; Female; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin gamma-Chains; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Immunoglobulin mu-Chains; Immunoglobulins; Immunologic Deficiency Syndromes; Male; Molecular Weight; Sodium Dodecyl Sulfate

Answers are beginning to emerge to the questions posed in the introduction to the preceding section. In vitro techniques that allow characterization of malignant cells have particular relevance when, as in Hodgkin's disease, the precise identity of the cells remains in doubt. Monolayer tissue cultures derived from Hodgkin's disease tumours and maintained as established cell lines have proven amenable to a variety of cytogenetic, immunological, enzymatic, and ultrastructural studies. Tissue culture experiemnts, in conjunction with meticulous immunological studies of individual Reed-Sternberg cells from non-cultured tumours, suggest that neoplastic cells of Hodgkin's disease are related to, and possibly derived from, cells of the monocyte-macrophage system. The lymphocytes that comprise an integral part of the cellular proliferation and form the basis for histological subclassification of the tumour could be a manifestation of cell-mediated immunity against this non-lymphoid malignant cell. The immunodeficiency of patients with untreated Hodgkin's disease of limited anatomical extent is not the primary event of the disorder and probably not related to the site at which the aetiological agent acts. The deficit does not result solely from impaired T-cell function and appears to arise as a consequence of excessive suppressor cell activity. Inhibitory monocyte-lymphocyte interactions may be one of the causes of defective cell-mediated immunity in Hodgkin's disease. The possible significance of elevated levels of circulating immune complexes in the serum of patients with Hodgkin's disease is indicated by the finding that such complexes react with cells of long-term monolayer tissue cultures derived from the tumour. Circulating immune complexes may be one source for intracellular immunoglobulin in non-cultured Hodgkin's disease cells. The presence of polyclonal immunoglobulin G on the membrane and within the cytoplasm of Reed-Sternberg cells could be due to in vivo binding and ingestion of immune complexes by such cells. The specificity of the interaction between soluble complement-containing immune complexes and neoplastic cells of Hodgkin's disease depends on the nature of the complexed antigen. The complexes could non-specifically attach via an Fc receptor or, if the complexed antigen is identical to a tumour cell antigen, the binding could be specific. If the immune complexes are tumour specific they could provide a source for isolation and identification of

Topics: Antigen-Antibody Complex; Antigens, Neoplasm; Binding Sites; Cell Transformation, Neoplastic; Cells, Cultured; Concanavalin A; Hodgkin Disease; Humans; Immunologic Deficiency Syndromes; Kinetics; Retroviridae; T-Lymphocytes, Regulatory

Topics: Cell Differentiation; Concanavalin A; Humans; Immunity, Cellular; Immunologic Deficiency Syndromes; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Psoriasis; T-Lymphocytes, Regulatory

Staphylococcus aureus protein A-positive bacteria have recently been proposed as selective B lymphocyte mitogens. We have studied the lymphocyte response to such mitogens in bacteria in normal subjects and in patients with primary immunodeficiencies. Patients with primary T cell defects show a normal response to protein A-positive bacteria and impaired responses to PHA and Con A. In contrast, patients with Bruton agammaglobulinaemia respond normally to these T cell mitogens but not to the bacteria. Thus, protein A-positive bacteria fulfil the criteria for being a T cell-independent B cell mitogen for human peripheral blood cells.

Topics: Adult; Agammaglobulinemia; B-Lymphocytes; Child; Child, Preschool; Concanavalin A; Female; Humans; Immunologic Deficiency Syndromes; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Phytohemagglutinins; Staphylococcal Protein A; Staphylococcus aureus; T-Lymphocytes; Thymidine

A plaque assay that detects human mononuclear blood cells producing immunoglobulin (Ig)M antibody to sheep erythrocytes was investigated for its usefulness in studying B-cell activation and regulation in 24 patients with humoral immunodeficiency. Cells from 3 of 15 patients with common variable agammaglobulinemia produced some plaques (range 40--160/10(6) cells; normal range 80--1240/10(6)), but those from the other 12, from all 7 with x-linked agammaglobulinemia and from the 2 with x-linked immunodeficiency with hyper-IgM failed to produce any detectable plaques. In co-cultures of patient and normal cells a very good correlation was seen between results of the plaque assay and an IgM biosynthesis assay in detecting excessive suppressor cell activity. Cells from 7 of 15 common variable agammaglobulinemics, from 3 of 7 x-linked agammaglobulinemics, and from both patients with hyper-IgM caused significant suppression of IgM biosynthesis and(or) plaque formation by normal cells. The observations in the last two groups and discordance for excess suppressor activity in identical twins with common variable agammaglobulinemia suggest that the activity develops secondarily to whatever their primary defects may be. Culturing non-T cells from common variable agammaglobulinemics exhibiting excessive suppressor cell activity with normal T cells resulted in plaque formation in four of five patients so studied; in all five the suppressor activity was found in the T-cell population. The availability of a plaque assay for the study of blood cells from immunodeficient patients provides a new probe to examine the cellular nature of such defects.

Topics: Adolescent; Adult; Agammaglobulinemia; Antibody-Producing Cells; B-Lymphocytes; Cell Count; Child; Child, Preschool; Concanavalin A; Hemolytic Plaque Technique; Humans; Immunoglobulin M; Immunologic Deficiency Syndromes; Infant; Phytohemagglutinins; Pokeweed Mitogens; Puromycin; Rosette Formation; T-Lymphocytes

We have investigated a new hypothesis for the association between adenosine deaminase (A.D.A.) deficiency and immunodeficiency--namely, that deoxyadenosine rather than adenosine (an equally effective A.D.A. substrate) is toxic to proliferating cells of lymphoid origin. This possibility was explored in mitogen-stimulated lymphocytes cultured with a potent A.D.A. inhibitor, E.H.N.A. (erythro-9[2-hydroxy-3-nonyl] adenine) to simulate A.D.A. deficiency. In this in-vitro system deoxyadenosine was inhibitory at much lower and more physiological concentrations (1 mumol/1), compared with adenosine (100 mumol/1).

Topics: Adenosine; Adenosine Deaminase; Adenosine Deaminase Inhibitors; Cell Survival; Cells, Cultured; Child; Concanavalin A; Cytotoxicity, Immunologic; Deoxyadenosines; Enzyme Inhibitors; Humans; Immunologic Deficiency Syndromes; In Vitro Techniques; Lectins; Lymphocyte Activation; Lymphocytes; Mitogens; Nucleoside Deaminases; Purine-Pyrimidine Metabolism, Inborn Errors

Topics: B-Lymphocytes; Concanavalin A; Cytotoxicity, Immunologic; Humans; Immune Sera; Immunologic Deficiency Syndromes; Immunosuppression Therapy; Lymphocyte Culture Test, Mixed; Lymphocytes; Lymphotoxin-alpha; Solubility; T-Lymphocytes

Delayed hypersensitivity (DH) responses of normal and immunodeficient horses were evaluated with antigens [dinitrochlorobenzene (DNCB), keyhole limpet hemocyanin (KLH)] and phytolectins [phytohemagglutinin (PHA), concanavalin A (Con A)]. Immunologically normal horses sensitized with 5 daily applications of 2 mg of DNCB developed positive skin reactions upon challenge with 0.4 mg of DNCB. The delayed onset of the reaction and the predominately mononuclear cell infiltration at the test site indicated these were DH reactions. Normal horses sensitized with 500 microgram of KLH and challenged with 100 microgram of KLH developed skin reactions appearing earlier and composed of neutrophils and mononuclear cells, suggesting involvement of both humor and cellular mechanisms. Arabian foals with combined immunodeficiency failed to respond visibly to either antigen. Intradermal injection of 50 microgram of PHA induced visible reactions in all normal horses tested. The slow development and the predominately mononuclear cell infiltrate of PHA reactions resembled DH responses to antigen. Reactions were induced by Con A in 15 of 16 normal adult horses and 7 of 14 normal foals. The reactions were rapid in onset and contained numerous eosinophils. All 6 foals with combined immunodeficiency failed to respond to PHA injection, whereas 5 of 6 did not respond to Con A. Based on the results of these studies, it appears that in vivo skin tests with PHA and DNCB can be used to screen horses for deficient T-lymphocyte responses.

Topics: Animals; Concanavalin A; Dinitrochlorobenzene; Dysgammaglobulinemia; Hemocyanins; Horse Diseases; Horses; Hypersensitivity, Delayed; Immunoglobulin M; Immunologic Deficiency Syndromes; Lectins; Lymphocyte Activation; Skin Tests

Topics: Adolescent; Antigens, Bacterial; Antigens, Fungal; Cells, Cultured; Concanavalin A; Female; Humans; Immunologic Deficiency Syndromes; Lymphocyte Activation; Lymphocytes; Phytohemagglutinins

We studied the immunocompetence of 6 healthy twins, whose monozygotic or dizygotic same-sexed twin partner had died from Hodgkin's disease. Lymphocyte DNA synthesis induced by concanavalin A was markedly reduced at 3 different concentrations in all twins compared to an age-matched group of healthy controls. The lymphocyte response to pokeweed mitogen and to phytohaemagglutinin was also impaired. PPD induced lymphocyte DNA synthesis was low in 3 twins and correlated well with their delayed skin hypersensitivity to the antigen. One twin was completely anergic to 3 different skin antigens. The mean total blood lymphocyte count did not differ from that of controls. There was no change in T or B-lymphocyte subpopulations. The presence of a functional lymphocyte deficiency in all twins strongly suggests that the immunodeficiency in Hodgkin's disease is partly caused by genetic and/or environmental factors.

Topics: Aged; Concanavalin A; Diseases in Twins; DNA; Female; Hodgkin Disease; Humans; Hypersensitivity, Delayed; Immunologic Deficiency Syndromes; Lectins; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Male; Middle Aged; Mitogens; Pregnancy; Skin Tests; Twins, Dizygotic; Twins, Monozygotic

Five patients with no detectable serum IgA (less than 20 mug/ml) and one patient with low serum IgA were compared to normal subjects. The number of circulating E-RFC was normal as was the lymphocyte DNA synthesis induced by PHA, Con A, and streptokinase-streptodornase. The patients had normal numbers of IgA-bearing lymphocytes and normal or increased numbers of B cells. Purified anti-immunoglobulin antibodies specific for IgG, IgA and IgM induced a normal lymphocyte DNA synthesis as did PWM. The patients' lymphocytes were able in vitro to transform into actively secreting IgA plasmocytes. This transformation was determined by counting the IgA and immunoglobulin-containing cells and then measuring the IgA and IgG secretion in the cultures. In some patients PWM was selectively suppressive in IgA B-cell transformation into IgA secreting cells; in the other patients PWM had no effect on the IgA B-cell differentiation. PWM enhanced the IgG secretion in the patients' cultures as well as IgA and IgG secretion in the normal controls.

Topics: Adult; Antibodies, Anti-Idiotypic; B-Lymphocytes; Child; Concanavalin A; DNA; Dysgammaglobulinemia; Female; Humans; Immunoglobulin A; Immunoglobulin A, Secretory; Immunoglobulin G; Immunologic Deficiency Syndromes; Lectins; Lymphocyte Activation; Male; T-Lymphocytes

A male infant with bilateral iris coloboma who had had repeated infections and malabsorption was studied. The levels of total lymphocytes and of T and B cells were normal or high, but IgA became undectable and IgG low, whereas IgM was normal. His lymphocytes did not respond to phytohemagglutinin (PHA), concanavalin A, pokeweed mitogen (PWM) or in mixed lymphocyte reactions (MLR), nor did they respond in vitro when thymosin was included in the test systems. He was skin-test-negative, even to dinitrochlorobenzene. His crudely isolated T lymphocytes and the supernatant of his PHA-stimulated lymphocytes inhibit the response of normal lymphocytes to PHA, PWM, and in MLR. During thymosin treatment skin test and lymphocyte reactivity to mitogen remained negative. He became faintly positive in MLR, and the suppressor activity in the supernatant of his PHA-stimulated lymphocytes no longer inhibited the response of normal lymphocytes to PHA, PWM, or in MLR. In parallel with thymosin treatment he showed quite marked clinical improvement.

Topics: B-Lymphocytes; Coloboma; Concanavalin A; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunologic Deficiency Syndromes; Infant; Iris; Lectins; Leukocyte Count; Lymphocyte Activation; Male; Mitogens; Skin Tests; T-Lymphocytes; Thymosin; Thymus Hormones

Topics: Adult; Animals; Antilymphocyte Serum; Bone Marrow; Bone Marrow Cells; Cattle; Cell Differentiation; Cell Separation; Cells, Cultured; Concanavalin A; Epitopes; Erythrocytes; Humans; Immune Adherence Reaction; Immunologic Deficiency Syndromes; Infant; Lectins; Male; Mitomycins; Parathyroid Glands; Sheep; Spleen; Syndrome; T-Lymphocytes; Thymidine; Thymosin; Thymus Extracts; Thymus Gland; Tissue Extracts; Transfer Factor; Tritium

Deficiency of adenosine deaminase (A.D.A.) occurs in an autosomal recessive form of severe combined immunodeficiency (S.C.I.D.). The role of this enzyme deficiency in the pathogenesis of the immune defects is not clear. A patient with A.D.A. S.C.I.D., studied during the first six weeks of life, was found to have B and T lymphocytes as well as 25% of normal lymphocyte responses to mitogens. This patient subsequently became severely lymphopenic with loss of mitogen responsiveness. Addition of calf-intestinal A.D.A. or human-erythrocyte A.D.A. to cultures of this patient's lymphocytes restored their ability to proliferate when stimulated with mitogens. These data indicate that A.D.A. deficiency is causally related to the cellular immune defects observed in A.D.A. S.C.I.D. and suggests a possible role for enzyme replacement in the therapy of this disorder.

Topics: Adenosine Deaminase; Animals; Cattle; Cell Division; Concanavalin A; Culture Techniques; Guanosine; Humans; Immunologic Deficiency Syndromes; Infant; Inosine; Lectins; Lymphocytes; Lymphopenia; Male; Mitogens; Nucleoside Deaminases; Plasma Cells; Uridine

Topics: Age Factors; Animals; Animals, Newborn; Antibody Formation; Antigens; Antigens, Bacterial; B-Lymphocytes; Body Weight; Bone Marrow Cells; Bone Marrow Transplantation; Brucella abortus; Bursa of Fabricius; Chickens; Chimera; Concanavalin A; Cyclophosphamide; Erythrocytes; Floxuridine; Idoxuridine; Immunologic Deficiency Syndromes; Iodine Radioisotopes; Lectins; Lymphocyte Activation; Lymphocyte Transfusion; Plant Lectins; Radiation Chimera; Sheep; Spleen; T-Lymphocytes; Thymus Gland; Transplantation, Homologous

Immunological and pathological studies in a case of partial Di George syndrome revealed an absence of parathyroids, a major hypoplasia of thymus but a relatively moderate decrease in peripheral T-lymphocyte numbers and functions. After in vitro incubation with normal thymus extracts, a normal proportion of bone marrow cells was induced to differentiate into cells with characteristics of T lymphocytes, thus establishing the presence of T-cell precursors in the patient's bone marrow.

Topics: Antigen-Antibody Reactions; Antilymphocyte Serum; Bone Marrow; Bone Marrow Cells; Concanavalin A; Female; Humans; Immunologic Deficiency Syndromes; Infant; Lymph Nodes; Lymphocyte Activation; Parathyroid Glands; Spleen; Syndrome; T-Lymphocytes; Thymus Gland; Transfer Factor

Blood lymphocytes from the majority of 33 unselected and untreated patients with Hodgkin's disease were deficient in T-lymphocytes and their DNA synthesis induced by concanvallin A mitogen and PPD antigen was impaired. The spontaneous DNA synthesis during the first 24 hours of culture was often raised. The prognostic role of the lymphocyte deficiency was evaluated in a follow-up 10-22 months after institution of therapy. The lymphocyte functions were more commonly abnormal in patients responding poorly to treatment (incomplete remission, relapse after treatment, or death) than in patients entering complete remission. The lymphocyte deficiency seems to give information about prognosis in Hodgkin's disease in addition to histopathology, clinical stage, B-symptoms and age.

Topics: Adult; Age Factors; Aged; Concanavalin A; DNA, Neoplasm; Follow-Up Studies; Hodgkin Disease; Humans; Immunologic Deficiency Syndromes; Middle Aged; Prognosis; T-Lymphocytes; Tuberculin

Cellular immunity was assessed in patients with operable squamous cell cancer of the head and neck using in vivo skin tests and in vitro lymphocyte stimulation tests. An expansion of a previous study continued to show that 30 per cent of patients with T1N0M0 lesions were DNCB-negative and that with more advanced lesions there was further impairment. A similar finding was observed in the blastogenic response to phytohemagglutinin and concanavalin A but not pokeweed mitogen. Overall, 40 per cent of patients with resectable cancer had a significant depression of the blastogenic responses to conconavalin A and phytohemagglutinin. This depression ranged from 15 per cent in patients with T1N0M0 lesions to 71 per cent in those with T3N0M0 lesions. Although this depression was more severe in patients with palpable cervical node metastases, it was related more to the size of the primary tumor than to the nodes per se. An exception occurred in patients with large fixed nodes in whom the depression of lymphocyte stimulation was most severe. The absolute T-cell count was also depressed in patients with head and neck cancer. This depression parallelled the lymphocyte stimulation results with phytohemagglutinin and conconavalin A and was progressive with increasing stage of disease. A correlation exists between DNCB negativity and early recurrence and shortened survival. Clinical follow-up study is too short to assess the correlation of in vitro immune function with these clinical prognostic factors.

Topics: Alcoholism; B-Lymphocytes; Carcinoma, Squamous Cell; Concanavalin A; Dinitrochlorobenzene; Fluorescent Antibody Technique; Head and Neck Neoplasms; Humans; Immune Adherence Reaction; Immunity, Cellular; Immunologic Deficiency Syndromes; Leukocyte Count; Lymphatic Metastasis; Mitogens; Skin Tests; T-Lymphocytes

Topics: Animals; Antibody Formation; Concanavalin A; Immunization; Immunologic Deficiency Syndromes; Mice; Mice, Inbred Strains; Ovalbumin; Phenotype; Reagins

Topics: Absorption; Adult; Agammaglobulinemia; Animals; Antibody Specificity; Antigens; Antilymphocyte Serum; Bone Marrow; Bone Marrow Cells; Cell Differentiation; Concanavalin A; Cytotoxicity Tests, Immunologic; Epitopes; Humans; Immune Adherence Reaction; Immunologic Deficiency Syndromes; Infant; Lectins; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Male; Rabbits; Spleen; Splenomegaly; T-Lymphocytes; Thymus Gland; Tissue Extracts

Topics: Aminohydrolases; Autopsy; Concanavalin A; Erythrocytes; Humans; Immunoglobulins; Immunologic Deficiency Syndromes; Infant; Lectins; Lymphocyte Activation; Male; Metabolism, Inborn Errors; Radiography; Spleen; Thymus Gland

Topics: Bone Marrow Examination; Candidiasis; Concanavalin A; Cytomegalovirus Infections; Fluorescent Antibody Technique; Histocompatibility Antigens; Humans; Hypersensitivity, Delayed; Immune Sera; Immunity, Maternally-Acquired; Immunoglobulins; Immunologic Deficiency Syndromes; Infant; Lectins; Lymph Nodes; Lymphocyte Activation; Male; Mitogens; Palatine Tonsil; Pedigree; Pneumonia, Pneumocystis; Thymidine; Tritium