title: Experimental autoimmune gastritis: mouse models of human organ-specific autoimmune disease.
abstract: Experimental autoimmune gastritis (EAG) is an excellent model of human autoimmune gastritis, the underlying cause of pernicious anaemia. Murine autoimmune gastritis replicates human gastritis in being characterized by a chronic inflammatory mononuclear cell infiltrate in the gastric mucosa, destruction of parietal and zymogenic cells, and autoantibodies to the alpha-and beta-subunits of the gastric H+/K+ ATPase. Disease is induced strain specifically in gastritis-susceptible BALB/c mice by methods with a greater variety than those for most other experimental autoimmune diseases. The disease is induced in the regional gastric lymph node in which pathogenic CD4+ T cells are recruited. The model provides an excellent illustration of regulation by CD4+CD25+T cells, and, indeed, the removal of such regulatory cells, e.g., by neonatal thymectomy, is thought to be a major mechanism by which disease can develop. The culprit T helper type 1 (Th1) CD4+ T cells recognize either the alpha- or beta-subunits of the gastric H+/K+ ATPase, but the beta-subunit appears to be the initiating autoantigen, while the alpha-subunit may have a role in perpetuating disease. Since no specific environmental modifiers are identifiable, the origins of the disease are intrinsic; this is illustrated by the capacity of a cytokine (GM-CSF)-dependent inflammatory stimulus in the stomach to initiate EAG, according to a transgenic model in which thymectomy is dispensible. Thus, EAG is an exquisite model for a reductionist analysis of the multiple elements that in combination induce autoimmunity in humans.
authors.affiliation: Department of Pathology and Immunology, Monash University Medical School, Prahran, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Field
authors.forename: M A
authors.initials: MA
authors.lastname: Biondo
authors.forename: K
authors.initials: K
authors.lastname: Murphy
authors.forename: F
authors.initials: F
authors.lastname: Alderuccio
authors.forename: B-H
authors.initials: BH
authors.lastname: Toh
mesh_terms: D000752:Anemia, Pernicious / Q000150:complications; D000818:Animals; D001327:Autoimmune Diseases / Q000209:etiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005756:Gastritis / Q000209:etiology* / Q000276:immunology; D016480:Helicobacter pylori / Q000472:pathogenicity; D006801:Humans; D008231:Lymphopenia / Q000139:chemically induced; D051379:Mice; D008822:Mice, Transgenic