Cytotoxic molecules expressed by intraepithelial lymphocytes may be involved in the pathogenesis of acute gastric mucosal lesions

Background:

Little information is available on the precise mechanisms leading to the development of acute gastric mucosal lesions (AGMLs). We investigated whether the pathologic mechanism of AGMLs resulting in damage to epithelial cells is associated with cytotoxic molecules expressed by activated intraepithelial lymphocytes (IELs). Methods: The expression of the lymphocyte markers, CD3, CD4, CD8, CD20, T-cell-restricted intracellular antigen (TIA)-1, and granzyme B (GrB)-7 in IELs and that of single-stranded DNA (ssDNA) in apoptotic epithelial cells were evaluated by immunohistochemistry, using endoscopic biopsy specimens from 20 patients with AGMLs and 20 controls. Results: The number of CD3- and CD8-positive IELs increased in AGML specimens when compared with controls, and this increase was accompanied by a concomitant increase in TIA-1-positive cells. The epithelial cell layers of AGML specimens contained more GrB-7-positive phenotypically activated cytotoxic T cells than those in controls. Apoptotic ssDNA-positive epithelial cells were detected more frequently in AGML specimens than in controls, a feature which was paralleled by an increase in GrB-7-positive IELs in the former group of specimens. Conclusions: The present study showed that activated cytotoxic IELs and apoptotic epithelial cells are increased in number in gastric mucosa affected with AGMLs. These results provide evidence that this condition could be categorized as apoptotic gastritis with activation of the innate immune response.