title: Failure of a protective major histocompatibility complex class II molecule to delete autoreactive T cells in autoimmune diabetes.
abstract: The association of major histocompatibility complex genes with autoimmune diseases is firmly established, but the mechanisms by which these genes confer resistance or susceptibility remain controversial. The controversy extends to the nonobese diabetic (NOD) mouse that develops disease similar to human insulin-dependent diabetes mellitus. The transgenic incorporation of certain class II major histocompatibility complex genes protects NOD mice from diabetes, and clonal deletion or functional silencing of autoreactive T cells has been proposed as the mechanism by which these molecules provide protection. We show that neither thymic deletion nor anergy of autoreactive T cells occurs in NOD mice transgenic for I-Ak. Autoreactive T cells are present, functional, and can transfer diabetes to appropriate NOD-recipient mice.
authors.affiliation: Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
authors.forename: R M
authors.initials: RM
authors.lastname: Slattery
authors.forename: J F
authors.initials: JF
authors.lastname: Miller
authors.forename: W R
authors.initials: WR
authors.lastname: Heath
authors.forename: B
authors.initials: B
authors.lastname: Charlton
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003520:Cyclophosphamide; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007111:Immunity, Cellular; D007116:Immunization, Passive; D007515:Islets of Langerhans / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD / Q000276:immunology; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D003520:Cyclophosphamide