Interleukin-2 does not overcome suppression of graft rejection by cyclosporin A: Effect of cyclosporin A on T cell properties in vivo

The most evident immunosuppressive effect of cyclosporin A (CsA) on T cells is suppression of interleukin-2 (IL-2) production through the suppression of type-2B serine/threonine-specific phosphatase, calcineurin, To test whether suppression of IL-2 production is a major mechanism of CsA-mediated suppression of allograft rejection, we treated allogeneic skin-grafted mice with CsA and IL-2, and observed that IL-2 did not override the suppressive effect of CsA. Specific cytotoxic T lymphocyte (CTL) activity and natural killer (NK) activity of the spleens were increased by treatment with IL-2, and CsA significantly suppressed the killing activity, We also found that CsA-treatment decreased the expression of Ick kinase of T cells and the production of IL-2 in response to concanavalin A (ConA), with minimum effect on IL-4 production, These results suggest that T cell dysfunctions other than decreased production of IL-2 are essential for suppressive effect of CsA on skin allograft rejection. (C) 1996 Academic Press, Inc.