The effects of immunosuppressants on FAS-mediated activation-induced cell death in human T lymphocytes.

Abstract

The effects of cyclosporin A (CsA) and methylprednisolone (MP) on Fas-mediated activation-induced cell death (FMAICD) of T lymphocytes were examined. T lymphocytes were activated with the immobilized anti-CD 3 and CD 28 monoclonal antibodies (MoAbs) (activation phase) and incubated further with the agonistic MoAb against Fas (death phase). Cell proliferation and DNA fragmentation were measured by XTT and diphenylamine assay. CsA in the activation phase inhibited DNA fragmentation mediated by anti-Fas MoAb but not MP. The combination of CsA and MP at the lower concentrations had little effect on FMAICD, although they had similar degrees of suppression on T lymphocyte proliferation as the maximum obtained by CsA or MP alone. In the death phase, MP induced apoptosis without 7C11 and CsA had no effects. These results indicate that the combination of CsA and MP at low concentrations could maintain FMAICD with the suppression on T lymphocyte proliferation.