SELECTIVE LOSS OF FUNCTIONAL ANTIDONOR CYTOLYTIC T-CELL PRECURSORS FOLLOWING DONOR-SPECIFIC BLOOD-TRANSFUSIONS IN LONG-TERM RENAL-ALLOGRAFT RECIPIENTS

Pretransplant administration of donor-specific blood transfusions prolongs the survival of HLA-disparate renal allografts to a level comparable to that of HLA-identical transplants. To test the hypothesis that DST recipients develop immunologic tolerance of their donors, we examined antidonor T cell immunity in a group of DST recipients with long-term well-functioning allografts. Limiting dilution analysis studies indicated that 5/14 long-term DST recipients exhibit a complete absence of detectable antidonor cytolytic T lymphocyte precursors (CTLp). In contrast, 4/4 long-term non-DST recipients who received conventional or cyclosporine immunosuppression exhibited significant levels of antidonor CTLp. Nonresponsive DST recipients retained the capacity to mount antidonor responses in mixed lymphocyte reactions and IL-2 production assays, and exhibited normal levels of CTLp directed to third-party antigens. Addition of exogenous IL-2 to cell-mediated lympholysis cultures did not restore antidonor CTL responses. In summary, our data suggest that the DST conditioning regimen induces a complete yet selective loss of functional antidonor CTLp in some long-term renal transplant recipients.