title: Immunopathogenesis, loss of T cell tolerance and genetics of autoimmune gastritis.
abstract: Over the past 10 years experimental autoimmune gastritis has been established as a highly defined model of organ-specific autoimmunity. Autoimmune gastritis represents one of the few autoimmune diseases in which the causative autoantigens, namely the gastric H/K ATPase alpha- and beta-subunits, are defined. Furthermore, it has been clearly established that a CD4+ T cell response to the H/K ATPase beta-subunit, in particular, is essential for the initiation of autoimmune gastritis. The immunopathology of autoimmune gastritis is due to a disruption of the normal developmental pathways of the mucosa, rather than a direct depletion of the end-stage parietal and zymogenic cells. CD4+CD25+ regulatory T cells were first described in experimental autoimmune gastritis and there has been a recent explosion of interest in the potential role of these immunoregulatory T cells in protection against a variety of autoimmune diseases. The availability of H/K ATPase deficient mice has begun to provide considerable insight into the basis for tolerance to the gastric autoantigens. Experimental autoimmune gastritis has also provided valuable insight into our understanding of the genetics of disease susceptibility and four distinct genetic regions have been identified which confer susceptibility to this organ-specific disease. The highlights of these recent advances are the subject of this review.
authors.affiliation: The Russell Grimwade School of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Ian R
authors.initials: IR
authors.lastname: van Driel
authors.forename: Alan G
authors.initials: AG
authors.lastname: Baxter
authors.forename: Karen L
authors.initials: KL
authors.lastname: Laurie
authors.forename: Tricia D
authors.initials: TD
authors.lastname: Zwar
authors.forename: Nicole L
authors.initials: NL
authors.lastname: La Gruta
authors.forename: Louise M
authors.initials: LM
authors.lastname: Judd
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Scarff
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Silveira
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gleeson
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics; D001327:Autoimmune Diseases / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005753:Gastric Mucosa / Q000254:growth & development / Q000276:immunology / Q000473:pathology; D005756:Gastritis / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D017506:H(+)-K(+)-Exchanging ATPase / Q000235:genetics / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D051379:Mice
chemical_list: D001324:Autoantigens; D017506:H(+)-K(+)-Exchanging ATPase