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.
Hadley
G A
GA
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110.
Anderson
C B
CB
Mohanakumar
T
T
D001803:Blood Transfusion; D003602:Cytotoxicity, Immunologic; D006410:Hematopoiesis; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D016030:Kidney Transplantation / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013997:Time Factors; D014019:Tissue Donors