Concanavalin A-induced Suppressor Cell Activity Research Articles

Concanavalin a-induced suppressor cell activity in patients with renal cell carcinoma

Concanavalin A (Con A)-induced suppressor cell activity against the proliferative response of autologous lymphocytes to phytohemagglutinin was examined in peripheral blood lymphocytes derived from 12 normal control subjects and 25 patients with renal cell carcinoma (RCC). The Con A-induced suppressor cell activity in patients with RCC (23.4 +/- 21.4%) was significantly higher than that in control subjects (9.7 +/- 10.7%, P less than 0.05). No significant difference between the degree of suppressor cell activity and stage of disease, grade of malignancy, or cell type was found, although the suppressor activity in patients with tumor microscopically infiltrated by lymphocytes was significantly higher than in patients without lymphocyte-infiltration into the tumor (P less than 0.05). Furthermore, compared with control subjects, Con A-induced suppressor activity in patients with high stage and in those with lymphocyte infiltration into the tumor was significantly higher (P less than 0.05 and P less than 0.01, respectively). In conclusion, because patients with RCC have high suppressor cell activity, abrogation of this activity may be necessary to treat the RCC.

Increased concanavalin A-induced suppressor cell activity in humans with occupational lead exposure

E-rosette-forming cells (E-RFC), mitogen-induced blast transformation, OKT4+, OKT8+ cells, and their ratio were found to be normal in 10 subjects chronically exposed to lead with blood levels of 40-51 micrograms%. However, concanavalin A (Con A)-induced suppressor cell activity (SCA) in these subjects was significantly greater than in normal matched controls. The clinical relevance of this observation is not clear, but it may have some bearing on the various immunologic defects described in lead exposure.

Immune functions in Parkinson's disease lymphocyte subsets, concanavalin A-induced suppressor cell activity and in vitro immunoglobulin production

Immune abnormalities, including the occurrence of autoantibodies against neural structures, diminished numbers of peripheral blood lymphocytes and reduced mitogen responses have been observed in patients with Parkinson's disease. In this study, we found that among the peripheral blood mononuclear cells (PBMNC) of patients with Parkinson's disease, there is a reduced number of cells spontaneously secreting immunoglobulins (Ig). After pokeweed mitogen stimulation, PBMNCs from patients with advanced Parkinson's disease had decreased capacity to elaborate Igs in vitro. In addition, there was evidence suggesting that OKT 4 + ( helper inducer ) subset may be decreased in Parkinson's disease along with disordered concanavalin A-induced suppressor cell activity. The findings do not primarily suggest an autoimmune pathogenesis of Parkinson's disease. The immune changes now observed partially resemble those seen in normal ageing, though being quantitatively exaggerated in Parkinson's disease. It is suggested that immune abnormalities in Parkinson's disease may result from disordered neural-immune regulation.

Effects of long‐term procainamide therapy on immunoglobulin synthesis

Procainamide is a potent inducer of autoantibodies. In order to evaluate the immunologic effects of this drug in vivo, 23 cardiac disease patients who had received procainamide for at least 6 months and an equal number of matched cardiac disease control subjects were studied, and percentage of circulating T cell subsets, concanavalin A-induced suppressor cell activity, and pokeweed mitogen--stimulated generation of immunoglobulin-secreting cells was quantitated. There was no significant difference between patient and control groups in the percentage of T cell subsets defined by OKT4 and OKT8 monoclonal antibodies or in concanavalin A-induced suppressor cell activity. The numbers of pokeweed mitogen--induced immunoglobulin-secreting cells were markedly decreased in the patient group, as measured by the protein A-augmented reverse hemolytic plaque assay (3,000 +/- 644, mean +/- SEM in patients versus 10,826 +/- 1,529, mean +/- SEM in control subjects, P less than 0.005). Removal of the adherent cell fraction did not improve the hyporesponsiveness. When B and T cell fractions of 6 patients were mixed with normal T and B cell fractions, all of the patients demonstrated diminished B cell responses, and one-half also had diminished T cell responses. Addition of patient adherent cells to a co-culture of normal B cells with deficient patient T cells restored plaque formation to normal levels, suggesting that the T cell defect was correctable by a macrophage-derived factor. The data obtained suggest that procainamide exerts an immuno-suppressive action on both B and T cell function in patients receiving this drug.

Defective concanavalin A-induced suppressor cell activity in lupus nephritis.

To determine whether patients with systemic lupus erythematosus (SLE) and active nephritis have more profound defects in suppressor cell activity, we studied concanavalin A (Con A)-induced suppressor cell activity (SCA) in 12 patients with lupus nephritis (LN) and 11 patients with chronic mesangial proliferative glomerulonephritis (CGN) without renal insufficiency. The levels of Con A-induced SCA were decreased in patients with LN compared with those in normal controls and those in CGN patients and lower in LN patients with the nephrotic syndrome (NS) than in those without NS. In contrast, the mean responses of Con-A-induced SCA in CGN patients with or without NS did not differ from normal subjects. These findings may lend further insight into the understanding of the immunoregulatory defect in LN.

Preservation of T-lymphocyte activity in autoimmune MRL- lpr mice treated with prostaglandin

MRL- lpr mice display immunoregulatory disturbances which are related to an early massive T-lymphocyte hyperplasia. Features of autoimmunity are rapidly progressive and these animals die from immune complex-mediated glomerulonephritis. Previous studies show that 15 methyl prostaglandin E 1 (PGE) treatment in MRL- lpr mice prolongs survival by preventing lymphoproliferation and the subsequent renal disease. The present study indicates that a major activity of this therapy stabilizes several T-cell functions. Both the age-related loss of the autologous mixed-lymphocyte reaction (AMLR) (Ly1 + 2,3 − dependent) and the concanavalin A-induced suppressor cell activity (Ly1 − 2,3 + dependent) remain intact. It is suggested that PGE preserves these T-cell functions by maintaining a more normal balance of T-cell subsets.

Effect of Corticosteroids on Suppressor-Cell Activity in Autoimmune and Viral Chronic Active Hepatitis

We detected a severe defect in concanavalin A-induced suppressor-cell activity in 22 patients with "autoimmune" chronic active hepatitis and in 26 patients with hepatitis B surface antigen (HBsAg)-positive chronic active hepatitis, as compared with 20 control subjects (P less than 0.01). Normal values were observed in 21 patients with "autoimmune" hepatitis in whom a remission had been induced and maintained by treatment with prednisolone. When lymphocytes from patients with autoimmune chronic active hepatitis were preincubated with low-dose prednisolone in vitro, suppressor-cell activity was substantially improved (P less than 0.01), but no clear effect of prednisolone was seen in cells from patients with HBsAg-positive chronic active hepatitis. The loss of suppressor-cell activity in chronic active hepatitis may allow liver damage to continue, and the reversal of the defect in the autoimmune form of the disease by administration of low-dose prednisolone provides a plausible explanation for the efficacy of this treatment. The contrasting in vitro responses to prednisolone in autoimmune and HBsAg-positive chronic active hepatitis suggest that the fundamental nature of the suppressor-cell defect may be different in these two forms of the disease.

Deficiency of suppressor T-cells in insulin-dependent diabetes mellitus: An analysis with monoclonal antibodies

Peripheral blood from 25 patients with insulin-dependent diabetes mellitus was examined for any alteration in the proportions and or functions of immunoregulatory T-cell subsets, defined with monoclonal antibodies. Ten of 25 (40%) patients demonstrated deficiency of OKT8 + (suppressor/cytotoxic) T-cells. Eight of these 10 patients had abnormally high ratios of OKT4 +/OKT8 + T-cells. Nine of 10 patients with abnormally low proportion of OKT8 + T-cells had deficient concanavalin A-induced suppressor cell activity against the proliferative response of autologous or allogeneic lymphocytes to phytohemagglutinin. No correlation was observed between the deficiency of suppressor T-cells and the control of diabetes. Therefore, it is likely that the deficiency of suppressor cells is related to insulin-dependent diabetes mellitus itself and not to the metabolic changes that are associated with diabetes mellitus. This study demonstrates both quantitative and qualitative deficiency of suppressor T-cells in at least some patients with insulin-dependent diabetes, that might play an important role in the pathogenesis and autoimmune manifestations of a proportion of patients with insulin-dependent diabetes mellitus.

Immunological Aspects of Psoriasis: V.T. Cell Subsets and Suppressor Cell Functions Regulating Immune Responses in Peripheral Blood

T cell subsets bearing Fc-receptors for either IgG (TG) or IgM (TM), and suppressor cell activity of peripheral blood mononuclear cells on in vitro lymphoproliferative responses were studied in patients with untreated psoriasis. The proportions of TG and TM cells were unmodified in 15 patients compared to 15 control subjects studied in parallel experiments. The concanavalin A-induced suppressor cell activity, as well as the spontaneous suppressor cell function of in vitro short-lived adherent cells, were in the normal range for 7 out of 8 psoriatic patients investigated. The data argue against the possibility that a generalized suppressor cell defect occurs in psoriasis.

Nonspecific Suppressor Cell Activity and Lymphocyte Response to β-Lactoglobulin in Cowʼs Milk Protein Hypersensitivity

beta-Lactoglobulin (BLG) is clinically the most frequent allergen in cow's milk protein hypersensitivity (CMPH). We therefore assessed its in vitro blastogenic effect on lymphocytes of patients suffering from CMPH. Twenty-two patients aged from 1 to 20 months were investigated. beta-Lactoglobulin produced a significantly (p less than 0.00003) higher blastogenic response in lymphocytes of patients with CMPH (mean stimulation index 7.7 +/- 0.7 SEM) than in 26 age-matched controls (2.7 +/- 0.4). This response was age related, being most marked in infants up to 5 months of age. Lymphocyte proliferation following stimulation with BLG can be a useful in vitro test in the diagnosis of CMPH. Because of this augmented lymphocyte response, we considered the possibility of a related defect in immune suppression. Nonspecific concanavalin A-induced suppressor cell activity was assessed in the above patient and control populations. Concanavalin A-induced suppressor cell activity was significantly (p less than 0.05) reduced in patients with CMPH. This too was most marked in the first few months of life. We suggest that the development of CMPH may be due to delayed maturation of a suppressor cell population.

Immunoregulation in hypersensitivity pneumonitis. I. Differences in T-cell and macrophage suppressor activity in symptomatic and asymptomatic pigeon breeders.

Cell-mediated immunity delineates symptomatic from asymptomatic pigeon breeders better than the presence of precipitating antibodies or HLA haptotypes. We therefore investigatedin vitro lymphocyte function in asymptomatic and symptomatic pigeon breeders. Peripheral blood, T, B, and adherent numbers were equal in both groups. Although the response to an optimum dose of concanavalin A was similar in both groups, the asymptomatic group revealed a reduced response to an optimum concentration of phytohemagglutinin and pokeweed mitogen. This decreased mitogen-induced proliferation was abrogated if cells from asymptomatic patients were precultured in medium alone for 48 hr before stimulation. A similar preincubation procedure, however, decreased the response to subsequent mitogenic stimulation in the symptomatic patients. As this suggested the possibility of heightened immunosuppression in the asymptomatic group, suppressor cells were studied. The numbers of FCγ-bearing T cells were similar in both groups and did not differ from control values. In addition, concanavalin A-induced suppressor-cell activity did not differ in either group. Nonetheless, fresh T cells, adherent cells, and peripheral blood mononuclear cells (PBMC) preincubated with pigeon serum decreased the response of preincubated autologous PBMC to mitogens and antigens in asymptomatics. A similar suppression did not occur in autoch-thonous cocultures of PBMC from symptomatic patients. These data suggest that there may be cellular suppressor influences in the asymptomatic group which are absent or nonfunctional in the symptomatic patients. Although this may be useful in distinguishing between the groups, the relationship of these suppressor cells, if any, to the pathogenesis of hypersensitivity pneumonitis awaits further study.

Spontaneous suppressor cell function in inflammatory bowel disease.

We investigated suppressor cell activity in the peripheral blood of 39 patients with inflammatory bowel disease (30 Crohn's disease and 9 ulcerative colitis) by the short-lived suppressor cell assay. There was a significant decrease in the suppressor cell activity in patients with inflammatory bowel disease (IBD), compared to 26 healthy subjects studied simultaneously. Five other patients with acute bacterial infections had normal suppressor activity. A group of 14 IBD patients was also investigated for concanavalin A-induced suppressor cell activity and decreased suppressor function was confirmed. A significant positive correlation was found between the two assays. A defect in suppressor cell activity may permit the expression or maintenance of immunologically mediated damage to the gut in IBD.

Multivariate analysis of T-cell functional defects and circulating serum factors in Hodgkin's disease.

A comprehensive immunologic and serologic analysis was performed on 31 untreated patients with Hodgkin's disease. Immune evaluations stressed T-cell functional activity and included traditional parameters (PHA responsiveness and delayed hypersensitivity skin reactivity), as well as newer functional assays (T-cell colony formation, chemotaxis, spontaneous and antibody-dependent cytotoxicity, and concanavalin A-induced suppressor cell activity (CISA). Serum factors included ferritin, prostaglandins, zinc, copper, immune complexes, and thymic hormone activity. Every patient exhibited at least one T-cell or serum abnormality. The greatest percentage of patients exhibited T-cell defects in chemotaxis (85%), colony formation (81%). and PHA reactivity (64%). Immune defects were more common with advanced disease but were not related to absolute T-cell or monocyte count, skin test anergy, or abnormalities of T mu/T gamma cell proportions. Linear relationships were identified among abnormalities in the three assays employing mononuclear cells (PHA, colony formation, CISA) which may have reflected the inhibitory influence of monocytes present in the mononuclear cell preparations. Low serum zinc correlated with marked impairment of T-cell chemotaxis. Elevated prostaglandins were associated with high PHA reactivity and with depressed colony formation. Our results indicate that many complex factors, including intrinsic T-cell defects, contribute to the impaired immunity associated with Hodgkin's disease.

Effect of BCG on Concanavalin A-induced Suppressor Cell Activity and Lymphocyte Stimulation in Stage I Melanoma

Suppressor cell activity was determined in 14 patients with stage I melanoma, treated with or without adjuvant Bacillus Calmette-Guerin (BCG) immunotherapy, and in 27 normal healthy volunteers. An in vitro test system was used in which peripheral blood mononuclear cells when stimulated with concanavalin A (ConA) significantly suppress proliferative responses of fresh autologous mononuclear cells. In addition, lymphocyte stimulation capacity to optimal and suboptimal concentrations of phytohemagglutinin (PHA) was determined in 44 BCG treated or not BCG treated melanoma patients and in 40 normal individuals. ConA induced suppressor cell activity was significantly (p less than 0.02) impaired in BCG treated melanoma patients (21.3 +/- 3.1% suppression) when compared to not BCG treated patients (39.8 +/- 5.6%) or to normals (38.3 +/- 9.3%). Lymphocyte stimulation capacity was depressed in all melanoma patients when suboptimal concentrations of PHA were used but was found to be not significantly altered at optimal concentration of PHA. The present study reveals that BCG immunotherapy impairs ConA induced suppressor cell activity in melanoma patients but does not influence lymphocyte stimulation capacity.

Concanavalin A-induced suppressor cell activity and in vitro immunoglobulin secretion in rheumatoid arthritis: correlation with clinical and immunological parameters.

Concanavalin A-induced suppressor cell activity was found moderately but significantly (P less than 0.05) decreased in RA patients treated with nonsteroidal antiinflammatory drugs (31 +/- 7% suppression) as compared to patients on remission-inducing drugs, such as gold, penicillamine, or chloroquine (51 +/- 6%) or to healthy individuals (50 +/- 6%). Also, lymphocytes from patients with antibodies to collagen mediated lower suppression (33 +/- 7%) than lymphocytes from patients without evidence for these autoantibodies (61 +/- 11%). No significant difference between patients and controls or between individual groups of patients were observed in regard to IgM and IgG secretion induced by pokeweed mitogen. Thus, although no indication for a severe derangement of regulatory cells in peripheral blood of RA patients could be observed in this study, a slight deficiency of ConA-inducible suppressor cells that may be reverted by remission-inducing drugs seems to be present in RA.

Concanavalin A-induced suppressor cell activity for T-cell proliferative responses: Autologous and allogeneic suppression in aging humans

Peripheral blood mononuclear cells from 48 healthy subjects of ages varying from 20 to 94 years were evaluated for the ability to generate suppressor cell activity following in vitro incubation with concanavalin A. The suppression of proliferative responses by autologous and young, allogeneic lymphocytes to phytohemagglutinin was assessed using suppressor/ responder cell ratios ( S R ) of 2:1 and 1:1 and by using a summation index. Inducible suppressor cell activity for autologous responder cells was comparable between 24 aged (76.0 ± 10.9 years) and 20 young (26.8 ± 4.6 years) subjects. However, aged subjects exhibited a significant decrease in suppressor cell activity ( S R = 1 ) when allogeneic responder cells were utilized. Our results indicate that autologous inducible suppressor cell activity is preserved in the aged population, whereas allogeneic activity is impaired.

Concanavalin A-induced suppressor cell activity in Hodgkin's disease

Peripheral blood mononuclear cells from 20 previously untreated adult patients with Hodgkin's disease were evaluated for the ability to induce suppressor cell activity following in vitro exposure to concanavalin A (Con A). Suppression of proliferative responses by autologous as well as normal allogeneic peripheral blood lymphocytes to the mitogen phytohemagglutinin (PHA) was assessed using suppressor/responder cell ratios of 2:1 and 1:1. The generation of Con A-induced suppressor cell activity (T-T suppression) was deficient in 35% of the patients ( 7 20 ) by the criteria employed. Peripheral blood leukocytes from 18% of patients ( 2 11 ) with localized disease (stages I and II), and 56% of patients ( 5 9 ) with widespread disease (stages III and IV) exhibited subnormal suppressor activity. There was no correlation between absolute lymphocyte count, absolute T-cell number, or proliferative response to PHA, and Con A-induced suppressor cell activity. This impaired ability to generate Con A-induced suppressor cells in Hodgkin's disease may reflect a functional T-cell deficit, or the suppressive influence of abnormal circulating monocytes.

Alteration in Concanavalin A-Induced Suppressor Cell Activity during Acute MHV-59 Hepatitis in Balb/c Mice

Alteration in Concanavalin A-Induced Suppressor Cell Activity during Acute MHV-59 Hepatitis in Balb/c Mice

Concanavalin A-induced suppressor cell activity opposing effects of hydrocortisone.

Concanavalin A-induced suppressor cell activity opposing effects of hydrocortisone.

Alteration in suppressor cell activity in chronic active hepatitis

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