Concanavalin A-induced Suppressor Research Articles

Immunological reactivity in children with central nervous system injuries immunized with adsorbed diphtheria-tetanus anatoxin M and measles virus vaccines

Immunological examination of children with cortical and cortical-subcortical injuries of the central nervous system showed some specific features of lymphocyte subpopulations, spontaneous and concanavalin A-induced suppressor activity, and spontaneous production of tumor necrosis factor α upon immunization with adsorbed diphtheria-tetanus anatoxin M or measles virus vaccine.

Suppression of cytochrome P450 gene expression in the livers of mice with concanavalin A-induced hepatitis

Cytochrome P450 (CYP) gene expression in the livers of mice with concanavalin A-induced hepatitis was examined. Treatment of mice with concanavalin A (10 mg/kg, i.v.) elevated plasma alanine aminotransaminase activity. In normal liver, CYP1A2, 3A and 2E1 mRNAs were expressed, and concanavalin A treatment differentially suppressed the expression of these CYP genes. Gadolinium chloride (40 mg/kg, i.p.) treatment, which inhibited the concanavalin A-induced elevation of plasma alanine aminotransferase activity without affecting concanavalin A-induced cytokine expression, counteracted the concanavalin A-induced suppression of CYP gene expression in the liver. Kupffer cell function or hepatic injury might contribute to the concanavalin A-induced suppression of CYP gene expression.

Sensory neurons regulate immunoglobulin secretion of spleen cells: cellular analysis of bidirectional communications between neurons and immune cells

The effects of primary sensory neurons in the dorsal root ganglia (DRG) on immunoglobulin (Ig)-secreting activity of spleen cells were investigated in culture. The conditioned medium (CM) of normal spleen cells stimulated DRG neurons to release neurokinin A which increased the number of Ig-secreting spleen cells. In contrast, the CM of concanavalin A-induced suppressor spleen cells induced the release of vasoactive intestinal peptide, an inhibitor of Ig secretion of spleen, from DRG neurons. These findings indicate that sensory neurons can help and suppress Ig secretion, and these bidirectional activities are controlled by the factors released from immune cells.

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.

Decreased CD45RA T cells in B-cell chronic lymphatic leukemia patients: correlation with disease stage

T-cell subsets CD4, CD8 and suppressor-inducers (CD45RA) were determined in 20 patients with B-cell chronic lymphatic leukemia (B- CLL). The proportion of CD4 and CD45RA was decreased when compared with T cells from normal subjects. CD8 was markedly increased. The activity of concanavalin A-induced suppressor cells was not significantly different from that of normal controls and was negatively correlated to the percentage of CD4 of B-CLL patients. The selective loss of CD45RA cells was more prominent in patients in advanced Rai stages of the disease (III to IV) than in early stages (0 to II). Six patients of the advanced stages group suffered from autoimmune hemolytic anemia, whereas no patient in the early stages of disease showed an autoimmune phenomenon. Our results may indicate a mechanism of autoimmunity in B- CLL similar to that of patients with autoimmune diseases.

Decreased CD45RA T Cells in B-Cell Chronic Lymphatic Leukemia Patients: Correlation With Disease Stage

T-cell subsets CD4, CD8 and suppressor-inducers (CD45RA) were determined in 20 patients with B-cell chronic lymphatic leukemia (B-CLL). The proportion of CD4 and CD45RA was decreased when compared with T cells from normal subjects. CD8 was markedly increased. The activity of concanavalin A-induced suppressor cells was not significantly different from that of normal controls and was negatively correlated to the percentage of CD4 of B-CLL patients. The selective loss of CD45RA cells was more prominent in patients in advanced Rai stages of the disease (III to IV) than in early stages (0 to II). Six patients of the advanced stages group suffered from autoimmune hemolytic anemia, whereas no patient in the early stages of disease showed an autoimmune phenomenon. Our results may indicate a mechanism of autoimmunity in B-CLL similar to that of patients with autoimmune diseases.

Cytotoxic and suppressor activities in patients with HTLV-I-associated myelopathy

Since there are several immune abnormalities and autoimmune-like features in human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/HTLV-I-associated tropical spastic paraparesis (HAM/TSP), we examined cytotoxic and suppressor cell functions in HAM/TSP. In this study, we assayed cell-mediated cytotoxicity of CD8 + T-cell lines established from cerebrospinal fluid lymphocytes of two patients with HAM and concanavalin A-induced suppressor cell activities of peripheral blood lymphocytes from five patients with HAM. Our study revealed that three of four CD8 + T-cell lines showed cytotoxic activities against autologous CD4 + T-cell lines infected with HTLV-I, and two of the three lines showed major histocompatibility complex class I-restricted cytotoxicity. We also demonstrated that the concanavalin A-induced suppressor function was not defective in HAM patients. Therefore, the immune abnormalities and autoimmune-like features observed in HAM/TSP may not result from defective cytotoxic or suppressor cell activities.

Effect of Radiotherapy on Natural Killer Activity in Childhood Acute Lymphoblastic Leukemia and Lymphoma.

Natural killer (NK) activity was increased after 24 Gy prophylactic cranial irradiation in childhood acute lymphoblastic leukemia (ALL), although there was no change in the percentage and the number of CD16 (Leu 11)(+) cells. NK activity as well as the percentage and the number of CD16(+) cells was not decreased in malignant lymphoma children treated with high doses of cervical irradiation (20 Gy <). A single dose of 20 Gy irradiation to lymphocytes augmented NK activity 1.4-fold in vitro in healthy individuals. Radiosensitive concanavalin A-induced suppressor T cells did not play a role in the suppression of NK activity, indicating that the enhanced NK activity induced by irradiation was not due to irradiation-induced impairments of suppressor T cells. The supernatants from irradiated lymphocytes slightly enhanced NK activity. In conclusion, the augmentation of NK activity by irradiation seems to be due to its direct effect on NK cells, not via NK suppressor cells but perhaps humoral factors play some role in this respect.

Inhibition of Immunoglobulin Synthesis In Vitro by Intravenous Lipid Emulsion (Intralipid)

Intravenous lipid emulsions depress lymphocyte proliferative responses and granulocyte function at concentrations found in the blood circulation during their administration. The effects of Intralipid, a widely used intravenous lipid emulsion, were measured on immunoglobulin production in vitro by pokeweed mitogen-activated lymphocytes as a test of B-cell function. Intralipid decreased IgG, IgM, and IgA production at soybean oil triglyceride concentrations of 2.5-20 mg/ml occurring in the blood circulation during Intralipid infusion. The effects on IgM and IgA production were highest and that on IgG production lowest. Hydrocortisone-sensitive and concanavalin A-inducible suppressor cells were more sensitive to Intralipid than other cell populations. In vivo Ig production may not be equally disturbed, inasmuch as Intralipid concentrations in the lymph nodes and the spleen may be lower than in the blood circulation. However, care should be taken to prevent Intralipid concentrations from becoming high enough to depress immune responses.

Development of an immunological staging system to prognosticate disease course in malignant cervical neoplasia

A multiparameter analysis of immune function was done on patients with squamous cell carcinoma of the uterine cervix to look for any variable(s) that could be correlated with the clinical stage of the disease. Five immunological variables, viz., CD4+ lymphocytes, CD4 CD8 ratio, natural killer cells, concanavalin A-induced suppressor index, and circulating immune complexes, were found to consistently vary with tumor load. When these variables were subjected to a multiple regression and multivariate analysis, an equation for a diagnostic index curve was derived. Application of this equation led to an immunological staging system which could be used as an excellent prognostic indicator. The immunological staging system showed that patients classified into a particular clinical (FIGO) stage behaved in a heterogeneous way immunologically and that patients developing recurrent disease could easily be identified from those remaining disease free, even before treatment. Subsequent follow-up of these patients further confirmed this observation, with the recurrent disease group easily identifiable. These results point out the immense potential of such a staging system and the importance of immunological evaluation in the preliminary management of patients with malignant cervical neoplasia.

T lymphocyte subsets, suppressor and contrasuppressor cell functions, and production of interleukin-2 in the peripheral blood of rheumatic fever patients and their apparently healthy siblings

We studied CD4 and CD8 T cell subsets, suppressor cell function, production of IL-2, and immune contrasuppressor cell activity in 21 patients with rheumatic fever (RF), both at the time of their first acute episode and 3 months later (recovery phase). As controls we studied their healthy sibling nearest in age, as well as age- and sex-matched unrelated normal subjects. In the acute phase we found CD4+ T cells to be high, concanavalin A-induced suppression to be low, and production of IL-2 to be significantly decreased, as compared to the normal unrelated controls. The addition of contrasuppressor cells (VV+) to cell cocultures resulted in an increase in proliferation by mononuclear cells (MNC) in response to streptococcal M antigen but not to C carbohydrate antigen. In the recovery phase, CD4+ T cells became normal, CD8+ T cells rose above normal, and the suppressor cell functions (concanavalin-A-induced and spontaneously expanded), as well as the production of IL-2, fell further. Siblings were found to have increased CD8+ T cells and decreased production of IL-2, as compared to the unrelated controls. These findings indicate that important immunoregulatory disturbances occur during the acute phase of rheumatic fever, some of which persist, accentuate, or change during the recovery phase. The findings in siblings could be related either to streptococcal infection or to familial immunoregulatory aberration.

A clinical and immunologic study of colchicine in asthma

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

Effect of Colchicine on Lymphocyte and Monocyte Function and Its Relation to Fibroblast Proliferation in Primary Biliary Cirrhosis

Lymphocyte and monocyte function was investigated in eight patients with primary biliary cirrhosis and in age-matched and sex-matched controls. In three of the eight cirrhotic patients, two were in the late stage of the disease (stage III) and concanavalin A-induced suppressor cell function was markedly decreased; it returned to normal levels after 1 mo of treatment consisting of 5 mg per week of orally administered colchicine. The relative percentage of T cell subsets (CD3, CD4 and CD8) and the mean percentage of the helper and the suppressor phenotype were similar in cirrhotic patients and in controls. Basal production of interleukin-1 activity by a monocyte-enriched fraction of peripheral blood mononuclear cells of cirrhotic patients was three-fold above control values: after stimulation with endotoxin, interleukin-1 values increased tenfold above basal levels in monocyte-enriched fraction of peripheral blood mononuclear cells of both normal and cirrhotic patients. Colchicine normalized the basal production of interleukin-1 and inhibited its stimulation by endotoxin by 50%. Culture supernatants of endotoxin-stimulated monocyte-enriched fraction of peripheral blood mononuclear cells increased the proliferation of cultured human skin fibroblasts by 50%. In contrast, supernatants from stimulated monocyte-enriched fraction of peripheral blood mononuclear cells obtained from colchicine-treated patients significantly inhibited fibroblast proliferation. These findings suggest that stimulated chronic inflammatory cells may play an important role in liver fibrosis. Some of the actions of colchicine could be related to its effects on lymphocyte and monocyte function.

Immunosuppressive properties of the Mycoplasma arthritidis T-cell mitogen in vivo: inhibition of proliferative responses to T-cell mitogens

We have previously shown that Mycoplasma arthritidis produces a soluble T-cell mitogen (MAM) which is active for most mouse strains that express the alpha chain of the I-E molecule (E alpha) encoded within the murine major histocompatibility complex. The lymphocytes from mice injected intravenously with the MAM exhibited a marked decrease in their ability to respond in vitro to MAM, to phytohemagglutinin, or to concanavalin A T-cell mitogens. Suppression could only be induced in MAM-responsive mouse strains and was most marked 1 to 4 days postinjection. Splenic and node cells and, to a lesser extent, thymic cells from MAM-injected mice could inhibit the ability of lymphocytes from normal mice to respond to MAM and lectin mitogens. A minimum of 2.5 x 10(4) viable cells was required for significant transfer of suppression, and no major histocompatibility complex restrictions were seen. Unlike concanavalin A-induced suppressor cells, which consist of a CD4-, CD8+ T-cell subset, suppressor cells induced by MAM were due to a CD4+ CD8- subset. We hypothesize that MAM may play a role in M. arthritidis-mediated disease by both its inflammatory and immunosuppressive properties.

Lymphocyte electrophoresis as an indicator of modulation of concanavalin A-induced suppressor T-cells in vivo by anti-cancer drugs

We have previously reported that concanavalin A (Con A)-induced suppressor T-cells in vivo are located in the lower electrophoretic mobility (EPM) zone as judged by the ratio of low mobility T-cells to high mobility T-cells (LMT/HMT ratio) in terms of lymphocyte electrophoresis, and that the administration of 5-fluorouracil (5-FU) eliminates their suppressor activity as assayed by Con A-induced lymphocyte blastogenesis in vitro. The current study was undertaken to clarify the relation between changes in EPM and suppressor activity of Con A-induced suppressor T-cells by the administration of antitumor drugs such as cyclophosphamide (CY) and 5-FU when assayed by production of anti-sheep red blood cell antibody in vitro. The pretreatment with 5-FU, but not CY, abrogated the suppressor activity of Con A-induced T-cells followed by restoration of the LMT/HMT ratio of Con A-induced T-cells to that of normal T-cells. These findings suggest that lymphocyte electrophoresis can be applied to an assay for screening immunomodulating agents in Con A-induced suppressor T-cells.

EFFECTS OF THIOPENTONE ON IMMUNOGLOBULIN PRODUCTION IN VITRO

Thiopentone is known to depress several granulocyte and lymphocyte functions. This study assessed the effects of thiopentone on IgG, IgM and IgA production by pokeweed mitogen-activated lymphocytes as a measure of B-lymphocyte function. Thiopentone decreased IgG production at greater than or equal to 25 micrograms ml-1 (91 mumol litre-1) concentrations and that of IgM and IgA at greater than or equal to 50 micrograms ml-1 (182 mumol litre-1) concentrations over 7 days of culture. Preincubation of lymphocytes for 1 h with thiopentone 0-500 micrograms ml-1 (0-1820 mumol litre-1) had no effect on immunoglobulin production, whereas incubation for 2 and 3 h decreased IgG and IgM production with toxic thiopentone concentrations of 500 micrograms ml-1. Hydrocortisone-sensitive suppressor cells and concanavalin A-inducible suppressor cells were more sensitive to high concentrations of thiopentone than the other cell populations. These findings may be important in patients receiving barbiturate treatment for cerebral protection.

Seasonal variation in suppressor T cell subsets and non‐specific suppressor cell function in hay fever sufferers

The helper/suppressor T cell ratio, as defined by monoclonal antibodies, was significantly higher in hay fever sufferers compared with controls (P less than 0.05), but only during or shortly after the pollen season. This was due to a reduction in the suppressor subset, which returned to control values in the winter. There was no significant difference in the non-specific concanavalin A-induced suppressor cell function compared with controls. The mean summer value was significantly lower than the winter value (P less than 0.05), but we cannot be sure that this was not the result of changes in laboratory conditions. No relationship was found between T cell subsets or suppressor cell function and total or specific IgE levels, or between T cell subsets and suppressor cell function. Our findings suggest that in hay fever, reduction in suppressor cell numbers and function is a secondary phenomenon.

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.

Effects of aflatoxin B 1 on murine lymphocytic functions

We recently reported on the immunotoxic effects of Aflatoxin B 1 (AFB 1), a secondary fungal metabolite of Aspergillus flavus in mice. The present paper describes the effect of AFB 1 on cellular functions in lymphocytes after in vivo or in vitro exposures. Male BALB/c mice received 0, 0.03, 0.145 or 0.7 mg/kg body weight of AFB 1 for 4 weeks. A dose-related decrease in DNA synthesis in lumphocyte cultures with or without the mitogens (lipopolysaccharide, phytohemagglutinin, pokeweed mitogen and concanavalin A) was observed. No effects on protein or ribonucleic acid synthesis were observed. There were dose-dependent decreases in peripheral leucocyte counts and natural killer cell function. Splenic lymphocytes from normal mice cultured with 10 −6 to 10 −4 M AFB 1 had decreased DNA synthesis at > 1 × 10 −5 M, 8 decreased protein synthesis at 10 −4 M and decreased RNA synthesis thesis at > 2.5 × 10 −5 M. In vitro addition of AFB 1 (>50 μM) reduced generation of concanavalin A-induced suppressor cells. The results suggest that AFB 1 had a direct and complex effect on lymphocytes and there is a differential sensitivity of various subpopulations.

Multiple sclerosis: in relapsing patients, immune functions vary with disease activity as assessed by MRI.

We have serially studied immunoglobulin G secretion in vitro, natural killer cell function, and concanavalin A-induced suppression in a group of seven patients with relapsing-remitting multiple sclerosis. In two patients, the development of a large clinically asymptomatic MRI lesion was accompanied by reductions in natural killer cell function, immunoglobulin G secretion in vitro (after pokeweed mitogen stimulation), and concanavalin A-induced suppression without parallel change in lymphocyte markers. We did not see this type of change in matched controls nor in stable multiple sclerosis studied serially. When clinical attacks appeared, there was no significant change in immune function. We conclude that changes in immune function correlate well with the activity of the disease as recognized by MRI. We suspect that decreased natural killer cell function, immunoglobulin G secretion in vitro, and concanavalin A-induced suppression are secondary to the large lesions recognized by MRI.