Frequency analysis of cyclosporine-sensitive cytotoxic T lymphocyte precursors

The influence of the immunosuppressant cyclosporine (CsA) on the antigen-driven activation of resting cytotoxic T lymphocyte precursors (CTL-p) and on the reactivation of mixed-lymphocyte-reaction-primed CTL, is analyzed at the clonal level. Using the limiting-dilution culture approach, we show that the majority (60-90%) of clones of CTL-p with specificity for given antigens are not activated in the presence of CsA; a minority (10-40%) of CTL-p are CsA-resistant. This is so for alloantigen-reactive CTL-p and major-histocompatibility-complex-restricted CTL-p with hapten specificity. In contrast, the frequency of CTL grown out of primed mixed lymphocyte culture cells is not influenced by CsA. Although CsA does not interfere with the short-term growth of I1-2-driven activated T cells, it may influence the expression of their cytolytic potential.