Autoimmune gastritis results in disruption of gastric epithelial cell development

We have investigated the underlying basis of the lesion in murine autoimmun e gastritis, a model of the human disease pernicious anemia. The disease is mediated by T lymphocytes and characterized by selective depletion of pari etal and zymogenic cells from the gastric unit (gland) together with gastri c epithelial cell hyperplasia. The gastric units of gastritic stomachs cont ained 2.3-fold more cells than normal and accumulated rapidly dividing, sho rt-lived gastric epithelial stem cells and mucous neck cells. Most of these immature cells failed to differentiate into end-stage cells but rather app eared to die by apoptosis. We also found no correlation between anti-pariet al cell autoantibody titers and the degree of gastric pathology, providing further evidence that autoantibodies do not play a direct role in the patho genesis of gastritis. Taken together, the normal developmental pathways of the gastric mucosa are disrupted in autoimmune gastritis, resulting in an a mplification of immature cell types. The differentiation of these immature cells appears to be blocked, contributing to depletion of end-stage cells. This scenario provides an explanation for depletion of not only parietal ce lls but also zymogenic cells even though they are not directly targeted by the immune system.