Experimental Autoimmune Gastritis: Mouse Models Of Human Organ-specific Autoimmune Disease.

Autor: Field, J., Biondo, M. A., Murphy, K., Alderuccio, F., Toh, B. H.
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Zdroj: International Reviews of Immunology; Jan-Apr2005, Vol. 24 Issue 1/2, p93-110, 18p, 1 Black and White Photograph, 1 Diagram, 2 Charts
Abstrakt: 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 α-and β-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 α- or β-subunits of the gastric H + /K + ATPase, but the β-subunit appears to be the initiating autoantigen, while the α-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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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