concanavalin-a and Lymphopenia

Topics: Animals; Bone Marrow Transplantation; Concanavalin A; Dogs; Graft vs Host Reaction; Heart Transplantation; Humans; Immune Tolerance; Immunity, Maternally-Acquired; Immunosuppression Therapy; Lymphocyte Culture Test, Mixed; Lymphocytes; Lymphopenia; Mice; Mice, Inbred Strains; Phytohemagglutinins; Radiation Chimera; Radiation Dosage; Radiotherapy; Radiotherapy Dosage; Skin Tests; Thymus Gland; Transplantation Immunology; Transplantation, Homologous

NF-κB is a crucial mediator of inflammatory and immune responses and a number of phytochemicals that can suppress this immune-regulatory transcription factor are known to have promising anti-inflammatory potential. However, we report that inducer of pro-inflammatory transcription factor NF-κB functions as an anti-inflammatory agent. Our findings reveal that a plant derived flavonoid baicalein could suppress mitogen induced T cell activation, proliferation and cytokine secretion. Treatment of CD4+ T cells with baicalein prior to transfer in to lymphopenic allogenic host significantly suppressed graft versus host disease. Interestingly, addition of baicalein to murine splenic lymphocytes induced DNA binding of NF-κB but did not suppress Concanavalin A induced NF-κB. Since baicalein did not inhibit NF-κB binding to DNA, we hypothesized that baicalein may be suppressing NF-κB trans-activation. Thioredoxin system is implicated in the regulation of NF-κB trans-activation potential and therefore inhibition of thioredoxin system may be responsible for suppression of NF-κB dependent genes. Baicalein not only inhibited TrxR activity in cell free system but also suppressed mitogen induced thioredoxin activity in the nuclear compartment of lymphocytes. Similar to baicalein, pharmacological inhibitors of thioredoxin system also could suppress mitogen induced T cell proliferation without inhibiting DNA binding of NF-κB. Further, activation of cellular thioredoxin system by the use of pharmacological activator or over-expression of thioredoxin could abrogate the anti-inflammatory action of baicalein. We propose a novel strategy using baicalein to limit NF-κB dependent inflammatory responses via inhibition of thioredoxin system.

Topics: Animals; Anti-Inflammatory Agents; Cell Line, Tumor; Cell Proliferation; Concanavalin A; Cytokines; DNA; Flavanones; Graft vs Host Disease; Lymphopenia; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mitogens; NF-kappa B; Protein Binding; Spleen; T-Lymphocytes; Thioredoxins; Transcriptional Activation

CD7 and CD28 are T cell Ig superfamily molecules that share common signaling mechanisms. To determine roles CD7 and CD28 might play in peripheral lymphocyte development and function, we have generated CD7/CD28-double-deficient mice. CD7- and CD28-single-deficient and CD7/CD28-double-deficient mice had normal levels of CD4 and CD8-single-positive T cells in thymus and spleen. However, CD28-deficient mice had decreased CD4+CD25+ T cells in spleen compared with wild-type mice, and CD7/CD28-double-deficient mice had decreased numbers of CD4+CD25+ T cells in both thymus and spleen compared with both wild-type and CD28-deficient mice. Functional studies demonstrated that CD4+CD25+ T cells from CD28-deficient and CD7/CD28-double-deficient mice could mediate suppression of CD3 mAb activation of CD4+CD25- wild-type T cells, but were less potent than wild-type CD4+CD25+ T regulatory cells. Thyroiditis developed in aged CD7/CD28-double-deficient mice (>1 year) that was not seen in age-matched control mice or single CD7- or CD28-deficient mice, thus suggesting in vivo loss of T regulatory cells allowed for the development of spontaneous thyroiditis. Taken together, these data demonstrated collaborative roles for both CD7 and CD28 in determination of number and function of CD4+CD25+ T regulatory cells in the thymus and peripheral immune sites and in the development of spontaneous thyroiditis.

Topics: Aging; Animals; Antibodies, Monoclonal; Antigen-Presenting Cells; Antigens, CD; Antigens, CD7; B7-1 Antigen; B7-2 Antigen; CD28 Antigens; CD3 Complex; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Division; Concanavalin A; Cytokines; Down-Regulation; Homeostasis; Immunophenotyping; Leukocyte Count; Lipopolysaccharides; Lymphocyte Count; Lymphopenia; Male; Membrane Glycoproteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Interleukin-2; Spleen; T-Lymphocyte Subsets; Thymus Gland; Thyroiditis

Foot and mouth disease virus (FMDV) is a picornavirus that causes an acute vesicular disease of cloven-hoofed animals. This virus continues to be a threat to livestock worldwide with outbreaks causing severe economic losses. The present study shows an analysis of immune system phenotype and function during the acute phase of FMDV infection in swine. In the first days of infection, a significant lymphopenia is observed that involves all T cell subsets, CD4(+), CD8(+), and CD4(+)/CD8(+). This marked lymphopenia is not a result of active infection of PBMC with the virus. Further, the response of residual peripheral blood T cells to the mitogen, Concanavalin A (ConA) is significantly reduced and occasionally eliminated. Animals usually resolve clinical signs of disease and develop antigen specific T cell responses to the virus and recover ConA reactivity. These characteristics of acute phase infection likely play an important role in viral pathogenesis, propagation and shedding of viral particles and may be targeted as a way of improving vaccine formulations.

Topics: Animals; Blood Cell Count; Concanavalin A; Flow Cytometry; Foot-and-Mouth Disease; Foot-and-Mouth Disease Virus; Lymphocyte Activation; Lymphocyte Subsets; Lymphopenia; Swine; Swine Diseases; T-Lymphocytes; Viremia

In previous work we have demonstrated that spleen mononuclear (Spm) cells from rats obtained 14 days after infection with Cryptococcus neoformans showed a diminution in proliferative response to Concanavalin A (Con A). In this study we further investigate some characteristics of the Spm cell population involved in the immunosuppressor phenomenon induced by C. neoformans. We observed that unstimulated Spm cells expressing T-cell receptor (TCR+) from infected rats were reduced in number after 96 h of culture. When the Spm cells from infected rats were stimulated with Con A, increased production of IL-10, reduced levels of IL-2, and decreased CD11a surface expression were shown. These immunosuppressor phenomena were also observed when the capsular polysaccharide, glucuronoxylomannan (GXM), was added to cultures of Spm cells from normal rats. However, GXM had a more pronounced effect in reducing the number of cells surviving in culture than that observed during infection and produced an increase in IL-4 production by Con-A-stimulated Spm cells. Addition of anti-IL-10 monoclonal antibody to cultures restored the lymphoproliferation of Spm cells from infected animals, indicating that IL-10 production is a suppressor mechanism of cell-mediated immunity during experimental infection. The results presented here indicate that at least two mechanisms mediate the nonspecific suppression in this model of cryptococcosis: IL-10 production and diminution of the number of T cells. GXM could be involved, since it has a pronounced effect in the reduction of Spm cells in vitro.

Topics: Animals; Concanavalin A; Cryptococcosis; Cryptococcus neoformans; Female; Immunity, Cellular; Interleukin-10; Interleukins; Lymphocyte Activation; Lymphocyte Subsets; Lymphopenia; Polysaccharides; Rats; Rats, Wistar; Receptors, Antigen, T-Cell; Spleen

The effect of 2.5 h of treadmill running at 75.6 +/- 0.9% VO2max on circulating leukocyte and lymphocyte subpopulations, epinephrine and cortisol concentrations, and the Con A-induced lymphocyte proliferative response was investigated in 22 experienced marathon runners (VO2max 57.9 +/- 1.1 ml.kg-1.min-1, age 38.7 +/- 1.5 yrs). Blood samples were taken 15 min before (07.15h) and immediately after exercise (10.00h), with three more samples taken during 6h of recovery (11.30, 13.00, 16.00h). Ten sedentary controls (34.7 +/- 1.0 ml.kg-1.min-1, 45.3 +/- 2.3 yrs) sat in the laboratory during testing and had their blood sampled at the same time points. Serum cortisol was elevated relative to controls for more than 3 h post-exercise, and correlated significantly with the 3-h post-exercise, and correlated neutrophil/lymphocyte ratio (r = 0.68, p < 0.001). The concanavalin A- (Con A) induced lymphocyte proliferative response was decreased relative to controls for more than 3 h post-exercise, and except for the immediate post-exercise time point, tended to parallel the decrease in T cell (CD3+) concentrations.

Topics: Adult; Cell Division; Concanavalin A; Epinephrine; Exercise Test; Humans; Hydrocortisone; Leukocyte Count; Leukocytes; Leukocytosis; Lymphocyte Activation; Lymphocyte Subsets; Lymphocytes; Lymphopenia; Male; Middle Aged; Neutropenia; Neutrophils; Oxygen Consumption; Running; T-Lymphocytes

Interleukin (IL)-7 is a potent stimulus for immature T and B cells and, to a lesser extent, mature T cells. We have inactivated the IL-7 gene in the mouse germline by using gene-targeting techniques to further understand the biology of IL-7. Mutant mice were highly lymphopenic in the peripheral blood and lymphoid organs. Bone marrow B lymphopoiesis was blocked at the transition from pro-B to pre-B cells. Thymic cellularity was reduced 20-fold, but retained normal distribution of CD4 and CD8. Splenic T cellularity was reduced 10-fold. Splenic B cells, also reduced in number, showed an abnormal population of immature B cells in adult animals. The remaining splenic populations of lymphocytes showed normal responsiveness to mitogenic stimuli. These data show that proper T and B cell development is dependent on IL-7. The IL-7-deficient mice are the first example of single cytokine-deficient mice that exhibit severe lymphoid abnormalities.

Topics: Animals; Base Sequence; Bone Marrow; Concanavalin A; Hematopoiesis; Hematopoietic Stem Cells; Interleukin-2; Interleukin-7; Lymphocyte Activation; Lymphocyte Count; Lymphocyte Subsets; Lymphoid Tissue; Lymphopenia; Mice; Mice, Knockout; Molecular Sequence Data; Recombinant Proteins; Spleen; Thymus Gland

Functional activity of T-lymphocyte suppressors (spontaneous and Con-A induced) has been studied in 17 patients with destructive pulmonary tuberculosis. Patients with ++fibrous-cavernous pulmonary tuberculosis were found to have characteristic disturbances of the regulatory lymphocyte function and a high index of theophylline-resistant E-RFC/theophylline-sensitive E-RFC in the presence of a general reduction of the immunity T-system indices. A higher balance of the regulatory lymphocytes was seen in patients with infiltrative tuberculosis in various disorders of the immunologic parameters.

Topics: Adult; Concanavalin A; Female; Humans; In Vitro Techniques; Leukocyte Count; Lymphocyte Activation; Lymphopenia; Male; Middle Aged; Rosette Formation; T-Lymphocytes; Tuberculosis, Pulmonary

To assess the value of feline immunodeficiency virus (FIV) infection as a model for human immunodeficiency virus (HIV) infection in man, we studied the impairment of certain immunological functions following natural or experimental FIV infection. Proliferative responses of peripheral blood mononuclear cells (PBMC) from symptomatic and asymptomatic cats after naturally or experimentally acquired FIV infection, induced by activation with the mitogens concanavalin A, pokeweed mitogen, or lipopolysaccharide or by stimulation with human interleukin-2 (IL-2), were significantly lower than the proliferative responses found with PBMC from noninfected control cats. Also IL-2 production levels of mitogen-activated PBMC from naturally infected symptomatic cats were significantly reduced. These data confirm that the pathogenesis of FIV infection in the cat, like HIV infection in man, is characterized by a serious malfunction of the immune system.

Topics: Animals; Cats; Concanavalin A; Disease Models, Animal; Feline Acquired Immunodeficiency Syndrome; HIV Infections; Humans; Immunodeficiency Virus, Feline; Interleukin-2; Leukocytes, Mononuclear; Lipopolysaccharides; Lymphocyte Activation; Lymphopenia; Pokeweed Mitogens

A study was designed to test the hypothesis that the lymphopenia caused by surgical stress in children may arise through selective depletion of one or more lymphocyte subsets. Blood samples from 22 children were taken pre- and postoperatively and 6, 12, 24, and 48 hours after surgery. Lymphocyte subsets were identified and counted using monoclonal antibodies and indirect immunofluorescence. By six hours postoperatively, the mean total lymphocyte count had fallen by 1.87 x 10(9)/L (P less than .01); this was largely due to the fall in helper T cells (1.53 x 10(9)/L, P less than .01) and both counts remained depressed for at least 48 hours. The helper:suppressor ratio also fell, from 3.42 to 1.92 (P less than .01), but had recovered by 48 hours. Lymphocyte function as measured by the response to pokeweed mitogen and concanavalin A was also reduced six hours postoperatively. These changes were independent of age. Major surgery in infants and children causes a selective reduction in helper T lymphocyte numbers, helper:suppressor ratio, and lymphocyte function. This suggests that immune competence in the immediate postoperative period in children is reduced, as it is in adults. The duration of this and its relationship to infection are not yet known.

Topics: Age Factors; Anesthesia, Inhalation; B-Lymphocytes; Cells, Cultured; Child; Child, Preschool; Concanavalin A; Humans; Infant; Infant, Newborn; Intraoperative Period; Leukocyte Count; Lymphocyte Activation; Lymphopenia; Pokeweed Mitogens; Surgical Procedures, Operative; T-Lymphocytes

Plasma corticosterone concentrations were increased by giving chickens implants containing corticosterone and the effects on lymphocyte numbers and lymphocyte responses to the mitogens, phytohaemagglutinin (PHA) and concanavalin A (con A), were measured. Raising plasma corticosterone caused a dose-related decrease in numbers of circulating lymphocytes. Blastogenic responses of lymphocytes in whole blood to PHA and con A were reduced and stimulation indices were decreased in those birds with raised circulating corticosterone. When the initial corticosterone-induced lymphocytopenia was taken into account it was evident that corticosterone depressed the responsiveness of the lymphocytes to PHA but not to con A. Additions of corticosterone to cultures of whole blood showed that PHA stimulation was more sensitive than con A stimulation to the inhibitory effects of corticosterone.

Topics: Animals; Chickens; Concanavalin A; Corticosterone; Dexamethasone; In Vitro Techniques; Lymphocyte Activation; Lymphopenia; Phytohemagglutinins

Spontaneous diabetes was fully prevented in 65 BB/hooded (BB/h) highly diabetes-prone hybrid rats that were given five intraperitoneal injections (25 to 30 x 10(6) cells/injection) of fresh splenocytes or concanavalin A (ConA)-activated cultured splenocytes (blasts) from the diabetes-free Wistar-Furth or Long-Evans strains during the first 2 postnatal wk. Rats remained under observation for up to the age of 180-200 days. Of 70 littermate controls that received no cell injections, 63 developed overt diabetes before the age of 180 days. One intraperitoneal injection (25 x 10(6) cells) of splenocytes or blasts given during the first 36 h after birth was not as effective as multiple injections in preventing overt diabetes. Mild insulitis was present in 4 of 59 "protected" rats; small, discrete mononuclear infiltrates in periductular connective tissue and/or between pancreatic acini were observed in 27. Nondiabetic BB/h rats that were protected with splenocytes or blasts from diabetes-free strains had the same degree of lymphopenia in peripheral blood and spleen as age-matched, insulin-treated diabetic BB/h rats, but the level of islet cell surface antibodies in their serum was significantly lower. The same neonatal injections that protected rats from the development of spontaneous diabetes were completely ineffective in preventing the adoptive transfer of diabetes later in life by the injection of blasts from acutely diabetic BB/h rats.

Topics: Acute Disease; Animals; Animals, Newborn; Autoantibodies; Concanavalin A; Diabetes Mellitus, Type 1; Lymphopenia; Rats; Rats, Inbred BB; Rats, Inbred Strains; Rats, Inbred WF; Spleen

This report describes alterations in functional responses to lectin-induced stimulation of peripheral blood lymphocytes and in the natural killer cell (NKC) activity, of college students, obtained during an outbreak of influenza A/Philippines/2/82(H3N2) virus infection. These results are compared with similar observations in college students with an acute, febrile, noninfluenzal respiratory illness that occurred during the same outbreak. The lymphopenia typical of influenza during acute illness was shown to be due to a reduction in both T and B cells without alteration in the CD4:CD8 ratio. In addition, phytohemagglutinin and concanavalin A responses were reduced and NKC activity was increased, while pokeweed mitogen reactivity was unaltered at the time of admission to the study. Patients with noninfluenzal illness showed early polymorphonuclear leukocytosis and a similar lymphopenia. Lymphocyte functions were virtually unchanged during acute illness in noninfluenza patients. The relatively specific alterations in lymphocyte responses to lectin-induced stimulation in influenza patients may indicate that the peripheral T cells are incapable of activation via the CD3 or CD2 activation pathways. In addition, increased NKC activity in the periphery may be reflective of increased NKC activity in the lung. Influenza-infected individuals with higher NKC activity at the time of admission to the study also took longer to recover. Finally, the early lymphopenia and the later neutropenia in the influenza-infected patient may represent migration of these cells from the circulation to the infected respiratory tract as a consequence of infection.

Topics: Concanavalin A; Humans; Influenza A virus; Influenza, Human; Interferons; Killer Cells, Natural; Lymphocyte Activation; Lymphocytes; Lymphopenia; Phytohemagglutinins; Pokeweed Mitogens; Respiratory Tract Infections

A study was made of the influence of T-cell mitogens (Con A and PHA) on the colony formation and differentiation of hemopoietic stem cells from normal and thymectomized mice, as well as of the relationship between the colony formation and the dose of injected thymocytes. The incubation of bone marrow cells with Con A and PHA was shown to inhibit the growth of spleen colonies. This inhibition is reduced by thymocytes within the dose intervals of 0.25-2.0 X 10(7) cells/mouse. Administration of these agents serially has led to the potentiation of inhibition effect and to the inability of thymocytes to reverse it. Con A and PHA exert no effect on the differentiation of stem cells. Incubation of the bone marrow cells from thymectomized mice with Con A is much less effective in the depression of colony formation, if compared with the treatment by intact bone marrow preparations. A reversed picture was observed using antiserum to mouse brain (RAMBS). It is proposed that regulation of stem cells is governed by different subpopulations of thymocytes.

Topics: Animals; Bone Marrow; Cell Differentiation; Cell Division; Concanavalin A; Dose-Response Relationship, Immunologic; Female; Hematopoietic Stem Cells; Lymphopenia; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mitogens; Phytohemagglutinins; Spleen; T-Lymphocytes; Thymectomy

Cell-mediated immunity (CMI) was evaluated in 8 patients with focal glomerular sclerosis (FGS), 50 patients suffering from chronic mesangial proliferative glomerulonephritis without renal insufficiency and 24 healthy controls. The following parameters were measured: delayed skin reactivity to purified protein derivative, circulating lymphocytes, lymphocyte cell-surface markers (neuraminidase-treated sheep erythrocyte and erythrocyte-antibody-complement rosettes) and functional markers (mitogenic responses to concanavalin A and phytohemagglutinin). The FGS patients with nephrotic syndrome (NS) had a significant depression in CMI, characterized by decreased responses of the lymphocytes to both concanavalin A and phytohemagglutinin, impaired delayed hypersensitivity to purified protein derivative and a decreased proportion of T lymphocytes as compared with normal subjects. In contrast, the levels of all CMI parameters studied in FGS patients in remission and in patients with chronic glomerulonephritis with or without NS did not differ from normal subjects. Thus, the majority of FGS patients with NS demonstrated an impaired response in a CMI assay system. The possible significance of these phenomena in the pathophysiology of FGS is discussed.

Topics: Adolescent; Adult; B-Lymphocytes; Concanavalin A; Female; Glomerulonephritis; Glomerulosclerosis, Focal Segmental; Humans; Hypersensitivity, Delayed; Intradermal Tests; Leukocyte Count; Lymphocyte Activation; Lymphopenia; Male; Middle Aged; Phytohemagglutinins; T-Lymphocytes

The BB rat has a marked T cell lymphocytopenia, with a near absence of peripheral "helper" T cells recognized by monoclonal antibody W3/25 (W3/25+ T cells). The lymphocytes of the BB rat's spleen and thymus were examined for the presence of W3/25+ T cells, which were found to be absent in the spleen but present in normal amounts in the thymus. Concanavalin A (Con A) responsiveness was absent in the BB's peripheral blood and spleen but present in the thymus. Thus, in these three lymphoid compartments, Con A responsiveness directly correlated with the presence or absence of W3/25+ T cells. These lymphocyte abnormalities in the BB rat are notably different from lymphocyte changes present in human type I diabetes.

Topics: Animals; Concanavalin A; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Lymphopenia; Rats; Rats, Inbred Strains; Spleen; Thymus Gland

Six pony foals, free of detectable serum neutralization (SN) antibody against equine herpesvirus type 1 by the standard virus-neutralization (VN) test, were inoculated with equine herpesvirus type 1. The ponies showed typical clinical signs of respiratory tract disease and developed a transient leukopenia, involving lymphocytes as well as neutrophils. The leukopenia reached its lowest point on postinoculation days (PID) 3 to 5 and then returned to base-line values by PID 8 to 10. On quantitation of lymphocyte subpopulations, T and B lymphocytes were decreased during the onset of leukopenia and then recouped during the recovery from leukopenia. However, the proportions of the T and B lymphocytes remained constant during the lymphopenia, ranging from 70% to 80% and 20% to 30%, respectively. The lymphocyte blastogenic response to mitogens increased to peak by PID 2 to 5 and then decreased to base line values or below by PID 7. Mitogen responses of T lymphocyte and mixed lymphocyte preparations were nearly similar. However, the responses of 2 ponies wee somewhat different from the responses of others in that there was an increase in the B lymphocytes in the range of 40% to 50% during the recovery phase of lymphopenia. Also, the 2 ponies' mixed lymphocyte response to mitogens was considerably higher and the T lymphocyte response to mitogen was lower as compared with that of mixed lymphocyte preparation. The importance of these 2 types of responses is discussed.

Topics: Acute Disease; Animals; Antibodies, Viral; B-Lymphocytes; Concanavalin A; Herpesviridae Infections; Herpesvirus 1, Equid; Horse Diseases; Horses; Leukocyte Count; Lymphopenia; Neutralization Tests; Phytohemagglutinins; Pokeweed Mitogens; Respiratory Tract Infections; T-Lymphocytes

We have previously reported a suppressor cell deficiency in four patients with familial Mediterranean fever (FMF). Since colchicine prevents FMF attacks, we tested the effect of colchicine (1 mg twice daily) on the suppressor cell function in three of these FMF patients. Proliferation of phytohaemagglutinin-stimulated responder cells co-cultured with concanavalin A-induced suppressor cells was measured. The three FMF patients' means (+/- s.e.m.) percentage suppression of normal responder cells was markedly low before treatment (6 +/- 2) but significantly (P less than 0.001) increased during colchicine treatment (41 +/- 5) to levels similar to normal volunteers' mean percentage suppression (44 +/- 3). Colchicine corrected their suppressor cell deficiency and prevented FMF attacks during the 15 months of treatment. These findings support the hypothesis that there may be an association between these three patients' suppressor cell deficiency and the pathogenesis of their disease. Furthermore, colchicine may be potentially useful in treating patients with other diseases associated with a suppressor cell deficiency.

Topics: Adult; Aged; Child; Colchicine; Concanavalin A; Familial Mediterranean Fever; Humans; Lymphocyte Activation; Lymphopenia; Male; T-Lymphocytes, Regulatory

The activity of the leucocyte inhibitory factor (LIF) stimulated with Concanavalin A was examined in chronic uraemic, haemodialysed patients. It was found that the LIF activity decreased in chronic uraemic patients as compared with the normal controls. The absolute T lymphocyte count and active E rosette formation also decreased. In in vitro experiments the authors have also examined the inhibitory effect of the so-called "middle-sized molecule" (MSM) on uraemic materials separated from the serum and the haemofiltrate. They observed that the materials with a molecular weight of 1000-1500 isolated both from the serum and the haemofiltrate significantly inhibited the Con A stimulated LIF production of normal lymphocytes and decreased the ratio of the active E rosette-forming T lymphocytes. On the basis of their experiments the MSM uraemic materials are considered responsible for the decreased immune reactivity of uraemic patients. These uraemic toxins can be dialysed.

Topics: Adult; Concanavalin A; Female; Humans; Leukocyte Count; Leukocyte Migration-Inhibitory Factors; Lymphokines; Lymphopenia; Male; Middle Aged; Renal Dialysis; Rosette Formation; T-Lymphocytes; Toxins, Biological; Uremia

Topics: B-Lymphocytes; Concanavalin A; Hemolytic Plaque Technique; Humans; Hydrocortisone; Immunosuppression Therapy; Kinetics; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Lymphopenia; Mitogens

Topics: Adult; Aged; Aging; Antilymphocyte Serum; Concanavalin A; DNA; Dose-Response Relationship, Immunologic; Hodgkin Disease; Humans; Lymphocyte Activation; Lymphopenia; Middle Aged; Time Factors

Topics: Adolescent; Adult; Cell Separation; Cells, Cultured; Child; Concanavalin A; Female; Hemolytic Plaque Technique; Humans; Lupus Erythematosus, Systemic; Lymphopenia; Male; Middle Aged; Pokeweed Mitogens; T-Lymphocytes

Cell-mediated immune responses were examined in 19 normal volunteers after intranasal administration of three strains of influenza A virus. Eight volunteers manifested respiratory tract illness along with fourfold rises of serum antibody and/or virus shedding. Samples of peripheral venous blood were obtained before and two days, five days, and four weeks after challenge. During acute illness, infected volunteers showed lymphopenia, which persisted for up to four weeks after challenge. The lymphopenia involved thymus-derived, bone marrow-derived, and null cells. Blastogenic responses of lymphocytes to stimulation with phytohemagglutinin, concanavalin A, and streptokinase-streptodornase were depressed during acute illness, and responses to phytohemagglutinin and concanavalin A remained depressed at four weeks after infection. Thus, influenza infection in humans can result in prolonged depression of numbers and functions of circulating lymphocytes.

Topics: Adolescent; Adult; Antibodies, Viral; B-Lymphocytes; Cells, Cultured; Concanavalin A; Humans; Immunity, Cellular; Influenza A virus; Influenza, Human; Lectins; Lymphocyte Activation; Lymphopenia; Mitogens; Streptodornase and Streptokinase; T-Lymphocytes

Total lymphocyte counts, and the percentage of T and B lymphocytes and monocytes in untreated patients with Hodgkin's disease were not significantly different from those observed in normal donors. At the completion of radiotherapy, the mean total lymphocyte count of 503/mm3 was 4 SD below the mean for normal controls. Although a group of 26 patients in continuous complete remission from 12 to 111 mo after radiation treatment regained normal total numbers of lymphocytes and monocytes, they exhibited a striking T lymphocytopenia and B lymphocytosis. Concomitantly, there was a significant increase of null (neither T nor B) lymphocytes. The response of peripheral blood lymphocytes to phytohemagglutinin, concanavalin A, and tetanus toxoid before treatment was significantly impaired. 1-10 yr after completion of treatment there seemed to be little or no recovery of these responses. The capacity of peripheral blood lymphocytes to respond to allo-antigens on foreign lymphocytes in vitro (mixed lymphocyte reaction) was normal in nine untreated patients. However, the mixed lymphocyte reaction was markedly impaired during the first 2 yr after treatment. There was a partial and progressive restoration of the mixed lymphocyte reaction during the next 3 yr, and normal responses were observed in patients in continuous complete remission for 5 yr or more. The in vivo response to dinitrochlorobenzene was also examined. 88% (15/17) of patients initially sensitive to dinitrochlorobenzene were anergic to the allergen at the completion of a course of radiotherapy, but nine of these regained their hypersensitivity response during the 1st yr after treatment. This data suggests that there is a sustained alteration in both the number and function of circulating T cells after radiation therapy in patients with Hodgkin's disease which may persist for as long as 10 yr after treatment. The restoration of cell mediated immune functions after radiotherapy is time dependent and its kinetics may differ for various T-cell functions. The implications of these findings with respect to the state of immunological competence after radiotherapy are discussed.

Topics: B-Lymphocytes; Concanavalin A; Dinitrochlorobenzene; Hodgkin Disease; Humans; Hypersensitivity, Delayed; Lectins; Leukocyte Count; Lymphocyte Culture Test, Mixed; Lymphocytes; Lymphopenia; Receptors, Antigen, B-Cell; T-Lymphocytes; Tetanus Toxoid; Time Factors

Topics: Animals; B-Lymphocytes; Concanavalin A; Cortisone; Heparin; Hydrocortisone; Lectins; Leukocyte Count; Lymphocyte Activation; Lymphocytes; Lymphopenia; Mice; T-Lymphocytes

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

The effect of corticosteroid administration on the redistribution of sirculating lymphocytes was studied in the guinea-pig, since this species closely resembles man in its relative resistance to the lymphopenic effect of corticosteroids. A single intravenous injection of hydrocortisone (either 10 mg or 100 mg/kg) caused a profound but transient lymphocytopenia which was maximal at 4 hours following injection, with a returnto normal counts by 24 hours. There was a proportionately greater decrease in circulating T lymphocytes compared to B lymphocytes, although both populations were diminished. Chronic cortisone acetate treatment (100 mg/kg subcutaneously for 7 days) caused a similiar pattern of lymphocytopenia except that it was sustained during the period of chronically elevated plasma cortisol levels. The lymphocytes remaining inthe circulation during the period of lymphocytopenia responded normally in vitro to the mitogens phytohemagglutinin, concanavalin A, and pokeweek mitogen. There was very littleeffect of corticosteroid administration on the numbers, proportions, or mitogenic response of splenic lymphocytes. There was a dramatic increase in the bone marrow of proportions and absolute numbers of lymphocytes bearing surface T-and B-cell markers, as well as a marked increase in response of bone marrow lymphocytes to mitogenic stimulation during the period of maximal circulating lymphocytopenia caused by the administration of corticosteroids, especially chronic cortisone acetate. There was a preferential homing of reinfused -51Cr-labelled syngeneic peripheral blood lymphocytes to the bone marrow of corticosteroid-treated recipients. These studies demonstrate aredistribution of circulating lymphocytes to the bone marrow during corticosteroid treatment, resulting in an increase in immunocompetence of this compartment, while the peripheral blood lymphocyte compartment is quantitatively immunosuppressed due to a lymphocytopenia.

Topics: Animals; B-Lymphocytes; Bone Marrow; Chromium Radioisotopes; Concanavalin A; Cortisone; Erythrocytes; Female; Guinea Pigs; Hydrocortisone; Immune Adherence Reaction; Immunosuppression Therapy; Lectins; Leukocyte Count; Lymphopenia; Rabbits; Sheep; T-Lymphocytes

The characteristics of cyclophosphamide-induced suppression of established ccll mediated immunity were studied in guinea pigs previously senstized to tuberculin. Cyclophosphamide treatment for 5 days produced a dose-dependent peripheral lymphoctopenia and disproportionatley greater neutrophenia which was particularly striking at high doses of 20 mg/kg per day(approximaetly 200 mg/kg-2 per day). Lymphoctes remianing in the circulation of cyclophosphamide treeated aniamls showed a doses-dependent reduction to both in vitro proliferactive and macrophage migration inhibitory factor responses to tuberculin compared to lymphocte responses of controls. Proliferative responses to phytohemaggultinin and concanavalin a were not significatly suppressed. Additional studies showed that cyclophosphamide suppressed the porliferactive and migration inhibitroy factor responses to tuberculin of lymph node and splenic as well as cirulating lymphocte populations. These studies showed that relatively short-term cyclophospamide administration produced immunosuppresion by quantitative as well as qualitative changes in lymphocyte populations. Significant suppresion of lymphocte function, howerver, was achived only with doses of cyclophoshamide which also produced a severe neutropenia.

Topics: Animals; Concanavalin A; Cyclophosphamide; Dose-Response Relationship, Drug; Guinea Pigs; Immunity, Cellular; Immunosuppression Therapy; Lectins; Leukocyte Count; Lymph Nodes; Lymphocytes; Lymphopenia; Macrophage Migration-Inhibitory Factors; Macrophages; Neutropenia; Spleen; Tuberculin