Effector mechanisms in organ-specific autoimmunity. I. Characterization of a CD8+ T cell line that mediates murine interstitial nephritis.
To further investigate mechanisms of cell-mediated tissue destruction in an organ-specific autoimmune disease, we have established and characterized a nephritogenic CD8+ T cell line. This target antigen-specific effector T cell line, M52, was derived from bulk populations of CD8+ T cells isolated from susceptible animals immunized to produce anti-tubular basement membrane (alpha TBM) disease. Our studies show that M52 retains the phenotypic and functional characteristics of nephritogenic T cells induced in vivo. M52 mediates antigen-specific delayed-type hypersensitivity (DTH) responses to the target antigen 3M-1, it is cytotoxic to 3M-1-expressing renal tubular epithelial cells in vitro, and it adoptively transfers interstitial nephritis to naive syngeneic recipients. Clonal analysis of these nephritogenic CD8+ T cells reveals distinct functional phenotypes within the M52 cell line. We have isolated a cytotoxic CD8+ clone, M52.26, which is not DTH-reactive to 3M-1, and multiple DTH-reactive clones which mediate less efficient cytotoxicity to 3M-1-expressing target cells. Cytofluorographic analysis of four randomly selected clones reveals alpha beta T cell receptor expression. Further characterization of these functionally distinct CD8+ T cell clones will help to define their respective roles in mediating tubular epithelial cell injury and the inflammatory lesion of autoimmune interstitial nephritis.
Meyers
C M
CM
Renal-Electrolyte Section, University of Pennsylvania, School of Medicine, Philadelphia 19104.
Kelly
C J
CJ
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D015551:Autoimmunity; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D015329:Gene Rearrangement, T-Lymphocyte; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006968:Hypersensitivity, Delayed; D007687:Kidney Tubules, Proximal / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009395:Nephritis, Interstitial / Q000276:immunology*; D009928:Organ Specificity; D011817:Rabbits; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I