Experimental autoimmune gastritis: mouse models of human organ-specific autoimmune disease

Int Rev Immunol. Jan-Apr 2005;24(1-2):93-110. doi: 10.1080/08830180590884585.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anemia, Pernicious / complications
  • Animals
  • Autoimmune Diseases / etiology*
  • CD4-Positive T-Lymphocytes / immunology
  • Disease Models, Animal*
  • Gastritis / etiology*
  • Gastritis / immunology
  • Helicobacter pylori / pathogenicity
  • Humans
  • Lymphopenia / chemically induced
  • Mice*
  • Mice, Transgenic