Experimental autoimmune gastritis: mouse models of human organ-specific autoimmune disease.
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.
Field
J
J
Department of Pathology and Immunology, Monash University Medical School, Prahran, Victoria, Australia.
Biondo
M A
MA
Murphy
K
K
Alderuccio
F
F
Toh
B-H
BH
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