Differential inhibition of primed alloreactive CTLs in vitro by clinically used concentrations of cyclosporine and FK506.

Previous studies in highly sensitized patients waiting for a renal transplant showed a lack of correlation between the formation of alloantibodies and the alloantigen specific cytotoxic T cell precursor frequency. The frequencies of CTLp against HLA class I antigens, toward which patients had formed antibodies (not acceptable mismatches, NAM), were similar to those against HLA antigens, toward which no antibodies were present (acceptable mismatches, AM). In more recent studies we tested whether the immunological triggering leading to antibody formation might have resulted in a different population of cytotoxic T cells. Limiting dilution assays performed in the absence or presence of antibodies against CD8 showed that CTL directed against NAM were significantly less inhibited by anti-CD8 compared with those directed against AM. Those "primed" CTL could also be distinguished from the more "naive" CTL on the basis of their resistance to cyclosporine. In contrast to CsA, therapeutic concentrations of FK506 were able to inhibit both "naive" and "primed" CTLs. The clinical relevance of these data is currently being investigated.