Effect of cyclosporin A on human lymphocyte responses in vitro. I. CsA allows for the expression of alloantigen-activated suppressor cells while preferentially inhibiting the induction of cytolytic effector lymphocytes in MLR

The effect of cyclosporin A (CsA) on in vitro human lymphocyte responses was assessed. CsA suppressed in a dose-dependent fashion, the lymphocyte response to stimulation with mitogens and with alloantigens in primary and secondary mixed lymphocyte reactions (MLR). In contrast, the action of cytolytic effector lymphocytes was not affected by this compound. Time-course kinetic studies indicated that the mitogen response was markedly dependent on the time of addition of CsA to the cultures. Inhibition of the lymphocyte response to alloantigens was less dependent upon the time of addition of CsA to the cultures. Preincubation with CsA did not markedly affect the ability of the lymphocytes to respond to mitogens and alloantigens, nor was there an overt cytotoxic action. In addition, CsA was shown to have a differential effect on the activation of cytotoxic and suppressor lymphocyte subpopulations in primary MLR. The induction of cytolytic lymphocytes was markedly suppressed by minimal amounts of CsA, whereas the induction of alloantigen-activated suppressor cells was much less inhibited by this agent. These results suggest that CsA treatment favors the induction of suppressor cell mechanisms as opposed to cytolytic effector cells in primary MLR. This may account for the ability of this drug to establish transplantation tolerance in vivo.