title: Self-thyroid epithelial cell (TEC)-reactive CD8+ T cell lines/clones derived from autoimmune thyroiditis lesions. They recognize self-thyroid antigens directly on TEC to exhibit T helper cell 1-type lymphokine production and cytotoxicity against TEC.
abstract: Self-thyroid epithelial cell (TEC)-reactive CD8+ and CD4+ T cell lines were established by culturing T cells that infiltrate in autoimmune thyroiditis lesions. We investigated the properties of CD8+ T cell lines and clones in comparison with previously characterized CD4+ T cell lines/clones. Although the recognition of self-Ag by anti-TEC CD4+ T cell lines/clones required the cooperation of syngeneic spleen cells as APC, a representative CD8+ line (N4C) was stimulated with syngeneic TEC in the absence of APC. Precise analysis of MHC restriction using N4C-derived clones revealed that CD8+ clones recognize self-Ag on TEC in the context of class I MHC molecules. Most CD8+ clones were also found to express TCR with V beta specificities that were different from those observed for anti-TEC CD4+ clones. N4C cells produced IL-2, IFN-gamma, and TNF-alpha beta, but not IL-4 and IL-5 after stimulation with TEC, thus exhibiting the profile of lymphokine production similar to that expressed by CD4+ Th1 on one hand, but on the other, they showed the functional property that has not been observed for anti-TEC CD4+ clones. Namely, they elicited appreciable levels of cytolytic effects on syngeneic TEC in a short-term (4-h) 51Cr release assay. Thus, these results indicate that self-TEC-reactive CD8+ T cell lines/clones recognize Ag directly on TEC in a class I MHC-restricted way so as to exhibit various functions including the Th1-like profile of lymphokine production and anti-TEC cytolysis. The results are also discussed in terms of the nature of self-Ag presented with class I MHC molecules on TEC, as well as the potential roles of anti-TEC CD8+ T cells in the pathogenesis of thyroiditis.
authors.affiliation: Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: S
authors.initials: S
authors.lastname: Sugihara
authors.forename: H
authors.initials: H
authors.lastname: Fujiwara
authors.forename: H
authors.initials: H
authors.lastname: Niimi
authors.forename: G M
authors.initials: GM
authors.lastname: Shearer
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D015703:Antigens, CD; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D018956:CD5 Antigens; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D004848:Epithelium / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000276:immunology; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011828:Radiation Chimera; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D013934:Thymectomy; D013961:Thyroid Gland / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D001324:Autoantigens; D018956:CD5 Antigens; D006183:H-2 Antigens; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma