Analysis of mononuclear cell infiltrate and cytokine production in murine autoimmune gastritis

Background & Aims: Murine autoimmune gastritis, induced by day-3 thymectomy, is characterized by cellular infiltrates and circulating autoantibodies to gastric hydrogen/potassium adenosine triphosphatase. The aim of this study was to analyze the cellular infiltrates and cytokines in autoimmune gastritis, Methods: Stomachs and blood samples from day-3 thymectomized BALB/c mice were obtained from 2 to 12 weeks after thymectomy for analysis, Results: At 4 weeks, the gastritic infiltrates were composed of macrophages and CD4(+) T cells, accompanied by major histocompatibility complex class II expression on gastric epithelial cells. Mucosal B cells, scant at 4 weeks, were abundant at 8 weeks, coincident with the peaking of autoantibodies to gastric hydrogen/potassium adenosine triphosphatase, CD8(+) T cells increased marginally during the 12 weeks, Mononuclear cells from diseased stomachs transferred gastritis to nu/nu recipients, At 4 weeks, interleukins 2, 3, 5, 6, and 10; interferon gamma; tumor necrosis factor alpha; and granulocyte-macrophage colony-stimulating factor were detected in gastritic mucosa, but interleukin 4 was not, Conclusions: The early lesion of autoimmune gastritis is composed of macrophages and CD4(+) T cells with major histocompatibility complex class II expression in gastric epithelial cells. Autoantibody production is a late event, Our results ave consistent with a lesion mediated by CD4(+) T cells producing a mix of Th1- and Th2-type cytokines.