Selective reduction of donor-specific cytotoxic T lymphocyte precursors in patients with a well-functioning kidney allograft.
We have recently developed a sensitive limiting dilution (LD) culture system to measure human alloreactive cytotoxic T lymphocyte precursors (CTL-p) in a given lymphoid cell population. We have now used this system to determine frequencies of donor HLA antigen-inducible CTL-p in the peripheral blood of human allograft recipients at various stages after transplantation. All patients (1 pancreas recipient and 9 kidney recipients) were on continuous cyclosporine treatment throughout the study. We report that, in patients with a well-functioning kidney graft (6/9), the number of donor-reactive CTL-p among peripheral blood lymphocytes decreased within 3-8 months after transplantation--in some cases (2/6) more than 10-fold. In contrast, frequencies of CTL-p with specificity for third-part HLA antigens remained largely unaltered in these patients. Furthermore, no decrease of donor-reactive CTL-p frequencies was seen in 3 of 4 patients showing clinical symptoms of graft rejection. These results indicate that functional clonal deletion of antigraft-reactive CTL-p may contribute to the state of graft tolerance in certain patients with a well-functioning kidney allograft.
D002478:Cells, Cultured; D003524:Cyclosporins / Q000008:administration & dosage; D006085:Graft Survival; D006680:HLA Antigens / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation; D007958:Leukocyte Count; D016035:Pancreas Transplantation; D011241:Prednisone / Q000008:administration & dosage; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014184:Transplantation, Homologous
D003524:Cyclosporins; D006680:HLA Antigens; D011241:Prednisone