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The action of levamisole on immunoglobulin production was investigated in pokeweed mitogen-stimulated cultures of B and T cells. Immunoglobulin production was measured by nephelometric methods using specific antisera to IgA, IgG and IgM. Levamisole was shown to have no effect on B lymphocytes but pretreatment of T lymphocytes with levamisole resulted in an increase in immunoglobulin production which was maximal at 10-6 M. The latter increase appeared to be due to an effect on suppressor T cells in that pretreatment of T cells depleted of suppressor cells (by irradiation or removal of T cells with receptors with IgG) did not result in an increase in immunoglobulin production. Similar effects of levamisole were demonstrated against suppressor cells induced by concanavalin A in vitro and against spontaneous suppressor cell activity in vivo. The effect of levamisole and irradiation on suppressor cell activity against particular classes of immunoglobulin varied between individuals. Suppressor cell activity against IgA production alone was demonstrated in six of 17 subjects whereas in the remainder, suppressor cell activity was either not detected or inhibited production of all three immunoglobulin classes. The implications of this action of levamisole for its effects in vivo are unknown, but the results appear consistent with many of the observed effects of the drug. Selection of patients with diseases associated with high suppressor cell activity may lead to more effective use of the drug. [ABSTRACT FROM AUTHOR]

A number of previous studies have described antibodies in normal sera reactive to human leukaemia cells. In the course of studies on humoral immunity to acute myeloid leukaemia (AML) cells it was noticed that sera from normal subjects were cytotoxic in complement lysis and leucocyte dependent antibody (LDA) assays to blood leucocytes from patients with AML in remission. Investigation of these reactions in eleven patients with acute leukaemia in complete or partial remission revealed that reactivity occurred most frequently between sera from normal blood group O or B subjects and leucocytes from patients of blood group A (five patients). Leucocytes from blood group O patients were largely unreactive. Blood leucocytes from five of six patients in relapse did not react with normal sera. Subsequent studies revealed that the antigens were detected only on T lymphocytes. Reactivity could be removed by absorption on red cells of blood group A but not sheep or Ox red blood cells suggesting the antigens concerned were closely related to blood group A antigens. Some reactivity with antisera to the blood group H antigens was also evident in these studies. Gel filtration studies indicated that lymphocyte dependent antibody mediated cytotoxicity was mediated by IgG antibodies while complement dependent lysis was mainly mediated by IgM antibodies. The biological significance of these findings has yet to be determined hut these results suggest that reactivity with blood group antigens needs to he considered in in vitro cytotoxicity. [ABSTRACT FROM AUTHOR]

The underlying basis for hypogammaglobulinaemia in patients with chronic lymphatic leukaemia (CLL) was investigated by measurement of immunoglobulin produced in vitro in cultures of pokeweed mitogen-stimulated B and T lymphocytes. B and T cells were separated by sheep red blood cell rosette techniques and, by culture of these cells from CLL patients in various combinations with B or T cells from normal subjects, it was possible to measure independently the function of B lymphocytes and the helper or suppressor function of T lymphocytes. By these methods it was found that the B lymphocytes of six of eight patients failed to produce immunoglobulins in vitro. B lymphocytes from two patients appeared to produce immunoglobulins in vitro. T lymphocytes from five of the eight patients had low or undetectable helper T cell function and in six patients their T lymphocytes had excessive suppressor activity in comparison to T lymphocyte populations from normal subjects. Whether the primary abnormality in the CLL T cell populations was a deficiency of helper T cells or excess of suppressor T cells was uncertain from these studies. These results suggest that immunoglobulin production by B lymphocytes from most patients with CLL was abnormal but also that T cells from CLL patients may be abnormal in respect to their role in immunoglobulin production at an early stage of the disease. These findings may assist in understanding the pathogenesis of this disease and lead to new approaches in treatment. [ABSTRACT FROM AUTHOR]

Lymphoid sub populations in the blood and rectal mucosa were studied in six patients with ulcerative colitis or Cohn's disease who had been treated for over three year with azathioprine. Serial assays were performed to observe the changes occurring up to 12 weeks after treatment with azathioprine was stooped. While the patients were on the drug tow lymphoid populations showed marked depression. These were the plasma cells of the rectal lamina procris, and blood lymphocytes with cytotoxic activity against antibody-sensitized tared cells ('k' cells). After stopping azathioprine, both population showed a rapid rise to reach near normal levels by 12 weeks, Most of the recovery occurred within 3-5 weeks. There was no significant change in circulating immunogolblin-staining cells which could be attributed to the drug. Nor was azathioprine shown to have any effect on the mitotic response of lymphocytes to phytohaemagglutinin. Three patients, however, gave very low or erratic responses to PHA, which may have been related either to their disease or to steroid therapy, These results are discussed in relation to the mode of action of purine analogues as immunosuppressive agents. [ABSTRACT FROM AUTHOR]