Evidence that antibody formation against a certain HLA alloantigen is associated not with a quantitative but with a qualitative change in the cytotoxic T cells recognizing the same antigen.

Previous studies in highly sensitized patients waiting for a renal transplant, showed a lack of correlation between the B cell and T cell allorepertoire. The cytotoxic T cell precursor (CTLp) frequencies against HLA-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 the present study we have 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 to AM. A possible clinical relevance of these findings is suggested by experiments showing that the CTL against NAM were also more resistant to cyclosporine than CTL against AM.