Induction and suppression of the cytotoxic activity of human lymphocytes in vitro by heterologous anti-lymphocyte serum.

Heterologous anti-lymphocyte sera were demonstrated to induce a cytotoxic potential in normal non-immunized human lymphocytes against allogeneic fibroblast target cells. The cytotoxicity-inducing capacity was restricted to certain dilutions of anti-lymphocytic serum above and below which no cytotoxic effect was obtained. This optimal concentration shifted towards higher dilutions in sera taken late during the immunization course. The antisera were shown to stimulate the DNA-synthesis in lymphocytes and to aggregate the lymphocytes to the target cells. The DNA-synthesis and the aggregation as well were maximal at the same dilution of anti-lymphocytic serum which induced cytotoxicity. No cytotoxic effect was demonstrable on sheep fibroblasts. It is, therefore, suggested that the anti-lymphocytic serum antibody induces lymphocyte-mediated cytotoxicity against allogeneic fibroblasts in a two step manner: it stimulates the lymphocytes into a cytotoxic state; it aggregates the human lymphocytes to the human fibroblasts by virtue of its bivalent structure. Anti-lymphocytic serum was also found to suppress the cytotoxic activity of lymphocytes induced by various non-specific agents, such as phytohaemagglutinin, streptolysin O and anti-lymphocytic serum itself. The mechanism for this inhibition is extensively discussed and it is suggested that anti-lymphocytic serum suppresses the reaction by coating the lymphocytes, thereby preventing the intimate contact between effector and target cell. A similar mechanism may operate and could be a partial explanation of the immunosuppressive effect of anti-lymphocytic serum. Purified 7S γ-globulin possessed all activities of the whole antiserum.