Cell-mediated cytotoxicity toward the donor in patients with well-functioning kidney grafts. Possible mechanism of specifically reduced cytotoxic response.
Patients with well-functioning kidney allografts from one-HLA-haplotype--mismatched related donors have strongly reduced donor-specific cell-mediated cytotoxicity 2-10 years after having received their grafts. This could also be demonstrated in secondary in vitro cell-mediated lympholysis (CML). Even though secondary donor-specific CML did not exceed 10% at an effector-to-target cell ratio of 50:1, specific lysis of donor target cells increased significantly with increasing effector cell concentrations. The weak cytotoxicity toward the donor could be enhanced neither through pool-cell stimulation nor by adding exogenous Interleukin 2 (IL-2) during the induction phase. Furthermore, growth factors were produced in the cultures during the induction of cytotoxic cells in concentrations comparable to those of the sibling control. Thus no evidence could be obtained that lack of IL-2 was causing the decreased cytotoxicity in these patients. Our studies indicate that in vivo depletion of cytotoxic cells with high lytic efficiency is probably the reason for the strongly reduced donor-specific cytotoxicity.
D003602:Cytotoxicity, Immunologic; D006133:Growth Substances / Q000096:biosynthesis; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology; D007668:Kidney / Q000502:physiology; D016030:Kidney Transplantation; D007700:Kinetics; D008213:Lymphocyte Activation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014019:Tissue Donors
D006133:Growth Substances; D006680:HLA Antigens; D007376:Interleukin-2