ABSTRACT
We have recently reviewed the historical, clinical, pathologic and immunologic features of autoimmune gastritis and pernicious anemia (1,2). Among the organ-specific autoimmune diseases, autoimmune gastritis par excellence, is the one condition in which the causative target autoantigen has been clearly identified. There is now compelling evidence from mouse models of autoimmune gastritis that the gastric H/K ATPase, the enzyme responsible for acidification of gastric juices, is the causative autoantigen. These mouse models of autoimmune gastritis demonstrate the condition is mediated solely by pathogenic CD4 T cells directed against this enzyme and that the pathogenic CD4 T cells are in turn controlled by a population of regulatory CD4 T cells. In this chapter, we provide a short overview of human autoimmune gastritis and pernicious anemia followed by a review of the molecular and cellular basis of CD4 T cell mediated tolerance and autoimmunity to the gastric H/K ATPase in the mouse.
