IMMUNOSUPPRESSANTS AND LYMPHOCYTE FUNCTION

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During the past year, our prime concentration has been on the in vitro reactivity of T lymphocytes from AIDS patients. For these studies, we have employed the T-colony assay. Our data, to date, indicate that lymphocyte colony formation is markedly reduced in this syndrome and in the epidemiologically related disorder ARC (AIDS-related complex), which in some patients is a prodromal phase of AIDS. The failure to grow T colonies did not closely correlate with several other parameters of T-cell immunity. Furthermore, it was shown that exogenous IL-2 was able to normalize the colony growth of most patients with the ARC syndrome. Although clonal responses of AIDS patients was increased significantly, the reactivity of most was still considerably less than controls. This correlated with reduced expression of IL-2 receptors on activated lymphocytes. Current investigations in AIDS concern: (1) the reactivity of isolated T-cell subsets; (2) the effects of other immunomodulators including IL-1, interferon, and recombinant IL-2; and (3) the suppressor effects of cells and sera from AIDS patients on the clonal growth of normal cells. In another study using the T-colony assay, the inhibitory activities of two commonly used immunosuppressants, cyclosporin and corticosteroids, were extensively evaluated. Both drugs caused a dose-related inhibition of clonal growth. The effects of steroids were reversed by exogenous IL-2 but not IL-1. By contrast, IL-2 failed to restore reactivity of cells treated with cyclosporin. Additional studies now in progress are evaluating the activities of prostaglandins and cytotoxic immunosuppressants including azathioprine, methotrexate, and 4-hydroxycyclophosphamide. The third phase of current studies is directed at factors controlling normal T lymphocyte colony growth. Isolated T cells do not respond to PHA; however, inclusion of IL-1, IL-2, or supernatants derived from short-term cultures of several tumor cell lines are able to act, in conjunction with this mitogen, to stimulate clonal growth. The tumor cell supernatants appear distinct from either IL-1 or IL-2. We are currently characterizing these active supernatants. (IS)