Immunogenicity of MHC class I alloantigens expressed on parenchymal cells in the human kidney.
The goal of the present study was to examine the capacity of human kidney cell lines (KCL) to elicit T cell responses to MHC class I alloantigens. KCL exhibited the phenotypic characteristics of tubular epithelial cells and were devoid of detectable contamination with leukocytes. Coculture of normal peripheral blood leukocytes (PBL) with allogeneic KCL elicited cytolytic T lymphocytes (CTL) that lysed the stimulating KCL but failed to lyse third-party KCL. Cell panel and antibody blocking studies demonstrated that the CTL were directed to the HLA class I alloantigens expressed on the KCL stimulators. Purified T cells completely failed to mount a CTL response to KCL, but the response could be reconstituted by supplementing the cultures with either autologous non-T cells or supernatant from a mixed lymphocyte culture (MLC). IL-2, but not IL-1, IL-4, IL-6, or gamma-interferon, restored the anti-KCL response, suggesting that IL-2 is the active factor in the MLC supernatant. Induction of class II antigens on the KCL stimulators with gamma-IFN failed to restore a CTL response, suggesting that KCL are deficient in a costimulatory factor important for class II restricted T helper responses. Nonetheless, our data demonstrate that parenchymal cells in the kidney are capable of presenting class I antigens to alloreactive T cells and, therefore, may contribute to the immunogenicity of renal allografts.
Hadley
G A
GA
Washington University School of Medicine, Department of Surgery, St. Louis, Missouri 63110.
Linders
B
B
Mohanakumar
T
T
D002460:Cell Line; D002478:Cells, Cultured; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D007668:Kidney / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
D015395:Histocompatibility Antigens Class I; D007519:Isoantigens