HLA regulates postrenal transplant CML nonreactivity.
Previous studies have shown that lymphocytes from renal allografted patients with a good functioning graft display donor-specific cell-mediated lympholysis nonreactivity (CML-NR) in vitro. To define whether the HLA system influences the occurrence of the CML-NR, immunogenetic studies were carried out. Posttransplant lymphocytes derived from CML-NR patients were stimulated in vitro with lymphocytes from unrelated healthy blood donors, who were selected for the presence or absence of kidney donor-specific HLA antigens. The presentation of kidney donor-specific HLA-B (and -C) antigens on the lymphocytes of unrelated blood donors resulted in cytolytic nonresponsiveness, whereas presentation of the kidney donor-specific HLA-A locus antigens on lymphocytes of the unrelated blood donors revealed no cytolytic nonresponsiveness. The results, as displayed by posttransplant lymphocytes of renal allografted patients, demonstrate that the kidney donor HLA-B (and -C) antigens are responsible for the in vitro-observed, donor-specific CML-NR. Consequently, presentation of cells from panel members matched to the kidney donor at the HLA-B locus suppresses the response towards HLA-A locus antigens. The in vitro-observed cytolytic nonresponsiveness appeared not to be due to an absence of specific cytotoxic T lymphocytes, because the nonresponsiveness can be abrogated by addition of exogenous IL 2.
D002999:Clone Cells / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D003602:Cytotoxicity, Immunologic; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006801:Humans; D007111:Immunity, Cellular; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D013154:Spleen / Q000166:cytology; D014019:Tissue Donors
D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens