title: Role of genetic factors in organ-specific autoimmune diseases induced by manipulating the thymus or T cells, and not self-antigens.
abstract: There are accumulating demonstrations that manipulation of the T-cell immune system, such as elimination of a particular T-cell subpopulation from the periphery or removal of the thymus during a critical neonatal period, can elicit activation/expansion of pathogenic self-reactive T cells from the remaining T cells and produce a wide spectrum of organ-specific autoimmune diseases in otherwise normal mice or rats. The genetic makeup of the hosts appears to play a key role in determining which self-reactive T-cell clones are prone to be activated under such circumstances, since a comparable degree of the immunologic abnormality elicits autoimmune disease in different spectrums of organs, with different incidences and severities, depending on the mouse or rat strains used. These findings indicate that one aspect of natural immunologic self-tolerance is maintained by a T cell-mediated control of potentially pathogenic self-reactive T cells in the periphery, and that defective control, caused by environmental insults or genetic abnormalities, suffices to cause autoimmune disease; furthermore, in the presence of such a T-cell abnormality, host genetic factors including MHC and non-MHC genes may determine the specificity and intensity of the autoimmune responses, and consequently the phenotype of the autoimmune disease.
authors.affiliation: Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: N
authors.initials: N
authors.lastname: Sakaguchi
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D012377:Rodentia; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D001324:Autoantigens