The influence of exogenous interleukin 2 (IL–2) on the immunosuppressive effect of cyclosporine in the mixed lymphocyte response (MLR) was examined. Results show that addition of exogenous IL–2 to a MLR containing graded doses of CsA (0.01–2.5 μg/ml) restored a normal proliferative response to alloantigens. In contrast, the effect of exogenous IL–2 on the induction of cytotoxic lymphocytes in primary MLR in the presence of CsA was variable. At the highest doses of CsA (0.5–2.5 μg/ml), no cytotoxic T cell activity could be detected, regardless of the presence of exogenous IL–2. However, at a lower dose of CsA (0.1 μg/ml) that routinely resulted in the total inhibition of cytotoxic T cell induction, addition of exogenous IL–2 resulted in significant levels of detectable cytotoxic T cell activity. The effect of time–sequential addition of CsA or CsA–plus–exogenous–IL–2 on the proliferative and CML responses in MLR was also examined. Results show that addition of CsA to ongoing primary MLR cultures within the first 48–96 hr of culture results in the significant inhibition of the proliferative and CML response in MLR. Addition of CsA–plus–exogenous–IL–2 to ongoing cultures resulted in no significant inhibition of the proliferative response. In contrast, addition of CsA–plus–exogenous–IL–2 within the first 4 hr of culture did not overcome the immunosuppressive effect of CsA. At 18 hr of culture addition of CsA resulted in complete suppression of the CML response, whereas the addition of CsA–plus–IL–2 resulted in significant levels of cytotoxicity. Thereafter addition of CsA–plus–IL–2 resulted in enhanced levels of cytotoxic T cell activity compared with cultures receiving CsA alone. Taken together, our results suggest that: (1) exogenous IL–2 can overcome the immunosuppressive effect of CsA on the proliferative response in MLR to alloantigens; (2) at high levels of CsA, IL–2 cannot overcome the immunosuppressive effect of CsA on the induction of cytotoxic T–lymphocytes; (3) there are.
ASJC Scopus subject areas