Effect of cyclosporine on secondary cytotoxic T lymphocyte responses

Cyclosporine, a potent immunosuppressive agent, inhibits the development of the cytotoxic response in a secondary mixed lymphocyte reaction (MLR) in a dose-dependent manner. Exogenous lymphokines can partially overcome this inhibition. We present evidence that the CsA-resistant cells detected in these responses represent an activated population of memory CTL precursors that require only lymphokines for clonal growth and that kill targets of the original stimulator type only. Recombinant IL-4, when used at high concentrations, can support the generation of CTL in the presence of CsA during a secondary MLR response. The magnitude of the cytotoxic response though is far below the maximal levels achieved either by saturating quantities of rIL-2 or a combination of subsaturable quantities of rIL-2 and rIL-4.