Human cytotoxic T lymphocytes. II. Frequency analysis of cyclosporin A-sensitive alloreactive cytotoxic T-lymphocyte precursors.

A limiting dilution (LD) culture system was used to investigate the effect of cyclosporin A (CsA) on the activation and differentiation of human alloreactive cytotoxic T-lymphocyte precursors (CTL-p). CsA reduced in a dose-dependent fashion the frequency of alloantigen-inducible CTL-p. With most normal individuals tested there was a 20- to 50-fold reduction of alloreactive CTL-p frequencies in the presence of 500-1000 ng/ml CsA. Both unseparated T cells and CD8+ T cells were CsA-sensitive under LD culture conditions. Importantly, however, alloreactive CTL-p from two out of 21 normal individuals were found to be largely CsA-resistant. CsA did not affect the growth of MLR-primed CTL in secondary LD culture. Furthermore, CsA slightly inhibited the cytolytic activity of some alloantigen-specific CTL clones. These results are discussed with respect to the clinical use of CsA in transplantation medicine.