Suppressor Activity Of Lymphocytes Research Articles

気管支喘息におけるリンパ球機能に関する研究

Cellular immunity in bronchial asthma has become essential for the regulation of various allergic reactions in the asthmatic attack. The function of peripheral blood lymphocytes of asthmatic patients was examined by the concanavalin A (Con A) induced suppressor cell assay. The suppressor activity of lymphocytes in mitogen-induced blastogenesis was shown to be decreased in patints with atopic and intractable asthma in comparison with the normal control. The suppressor activity in mite antigen induced lymphocyte blastogenesis was also decreased in patients with atopic asthma. Furthermore, the decrease of ConA induced suppressor activity correlated with the increase of serum IgE level in patients with atopic asthma.These findings indicate that the decreased suppressor cell activity is part of the mechanism of attack and may play an important role in the pathogenesis of bronchial asthma.

Enhancement of Suppressor T Cell Activity by Lymphocyte Promotiong Factor of Bordetella Pertussis

Lymphocyte promoting factor (LPF), a bioproduct of Bordetella pertussis shown previously to exert immunosuppressive effects, was examined for its effect on Concanavalin A (Con A) induced T lymphocyte suppressor activity by human lymphocytes. Suppressor cells (5 x 10(4) cells/well) first generated with Con A (10 micrograms/ml) for 24h were co-cultured with responder cells (5 x 10(4) cells/well) for another 72h in the presence of Con A (2.5, 5, 20 micrograms/ml). In this culture condition, LPF (20 micrograms) and/or histamine 10(-5) M or 10(-6) M/well were added for comparison. The suppressor activity was assessed by the reduction of the uptake of radioactivity of [3H] thymidine compared to that of Con A alone. Lymphocytes treated with LPF exhibited increase of suppression by 22 to 41%, while LPF and histamine (10(-5) M) together further increased the suppression by 35 to 63% compared to controls. Serial studies on cell population in the culture indicated OKT8(+) cells proliferated after day 6 in culture. These results indicated LPF exerts selective enhancement of T cell suppressor activity by 72h in culture, prior to cell expansion, and that activity can be further strengthened by sensitizing cells to histamine.

Modifying the biological response in acute myeloid leukemia. II. Effect of BCG and leukemic cells on lymphocyte response to mitogens, and on helper and suppressor activity.

Lymphocyte response to mitogens and to lymphocyte suppressor and monocyte helper activity was studied in 18 patients with acute myeloid leukemia in complete remission, and in 17 healthy controls. Ten patients were maintained with chemotherapy alone (CT), and eight received chemoimmunotherapy with BCG + leukemic cells (CIT). In late remission the mitogen responsiveness was increased in CT patients and decreased in CIT patients. No significant difference in lymphocyte suppressor activity could be demonstrated between patients and controls, or between CT and CIT. When autologous CIT monocytes were added to mitogen-stimulated lymphocytes they acted as helper cells. CT monocytes, in contrast, seemed to act as suppressor cells. Control monocytes also acted as helper cells, but to a significantly lesser degree than CIT monocytes.

Lymphocyte suppressor activity in patients with polyglandular failure

The Con-A—activated suppressor function of lymphocytes from polyglandular failure (PGF) patients in human mixed lymphocyte culture was compared to a normal population. As a group, PGF patients were found to have decreased suppressor activity: 67% of normal for autologous suppression, 45% of normal for heterologous. However, lymphocytes from most PGF patients have neither an absolute lack of suppressor activity nor an absolute inability to respond to suppression. The marked variability of assayed suppression, depending on the combination of stimulators and responder cells tested, limit the utility of this assay in defining individuals with abnormal suppressor function. One patient's lymphocytes were unique in that although suppression of heterologous cells was normal, suppression of her own cells was defective. Defective suppressor function may be related to the susceptibility of these patients to multiple autoimmune diseases.

Defective suppressor cell activity in cancer patients: a defect in immune regulation.

Although suppressor cells appear to be involved in the normal regulatory mechanism of the lymphoid system, they are also considered to have a role in the immunosuppression of certain malignancies. Suppressor activity of lymphocytes can be reproducibly measured by use of the mixed lymphocyte culture-mitogen interaction (MLC-M) in which the stimulating cell either is in the basal state or has been induced by Concanavalin A. This yields a quantitative measure of resting suppressor cell activity as well as the maximum generation of suppressor activity as induced by Con A. This test was performed, using autologous and allogenic cell combinations in a group of 13 cancer patients and 18 normal controls. Normal lymphocytes activated by Con A in 48-hour lymphocyte cultures significantly decreased the mitogenic response of lymphocytes from healthy, male donors to phytohemagglutinin (PHA), Con A, and Pokeweed mitogen (PWM) in both autologous and homologous systems. In contrast, Con A activated lymphocytes from cancer patients demonstrated diminished suppressor activity compared with controls in autologous (P less than 0.01), and allogenic (P less than 0.005) systems. There was a correlation between the degree of immunosuppression and suppressor cell activation: i.e., the patients most depressed generally had the lowest suppressor cell activation. Untreated lymphocytes from cancer patients also exerted suppressive effects on normal lymphocyte responses, suggesting an increased resting level of suppressor cells. These data suggest that in addition to having depressed cellular immune responses, cancer patients frequently have reduced capability to generate suppressor cell activity, which implies a generalized defect in this aspect of immune regulation.

Role of prostaglandin E2 in the induction of nonspecific T lymphocyte suppressor activity.

Activated human monocytes and concanavalin A (Con A)-activated T lymphocytes are known to suppress T and B lymphocyte proliferation and B cell maturation into immunoglobulin-producing cells. We have now shown that monocyte suppressive activity is predominantly mediated through release of prostaglandin E2 (PGE2), which is active only in the presence of a "short-lived," radiosensitive T lymphocyte subset. PGE2, at high concentration, can activate T suppressor lymphocytes (TS), which display the same characteristics as Con A-activated TS lymphocytes. Moreover, Con A activation of TS lymphocytes was obtained only in the presence of PGE2, as specific anti-PGE2 antiserum or indomethacin prevented TS activation; this suggested a double signal as a prerequisite for activation of the nonspecific TS cell subset. We propose that TS lymphocytes modified by Con A become sensitive to small amounts of PGE2 produced by monocytes that must be present during the Con A-stimulated activation phase of suppressive cells.

Suppressor activity of lymphocytes from patients with systemic lupus erythematosus

Lymphocytes from 16 patients with SLE disease were studied for their ability to proliferate and to induce stimulation of normal control allogeneic lymphocytes. In 14 patients, the PHA response was normal. A low proliferative response, however, was shown in MLC when patients lymphocytes were cultured with irradiated control cells. The immunological response of two other SLE patients displayed quite a different pattern. These two patients exhibited negative delayed hypersensitivity skin tests and had a low proliferative response of lymphocytes in PHA cultures and in a one-way as well as in a two-way MLC. The absence of reactivity was not due to a lack of responder cells but to the presence of a radio sensitive suppressor activity. In these two patients, however, the relationship between abnormal cell-mediated functions and SLE disease is unclear and may be circumstantial.