CD4+ CD8αα+ T cells in the gastric epithelium mediate chronic inflammation induced by Helicobacter felis

Abstract

CD4+ CD8αα+ double-positive intraepithelial T lymphocytes (DP T cells), a newly characterized subset of intraepithelial T cell, has been reported to contribute to local immunosuppression. However, whether DP T cells are present in Helicobacter. pylori-induced gastritis, and their relationship with disease prognosis remain to be elucidated. In this study, We established chronic gastritis models through Helicobacter felis (H. felis) infection. Gastric in ltrating lymphocytes were isolated from H. felis-induced gastritis mice and analyzed by ow cytometry. Our results suggest that DP T cells frequency in H. felis-induced gastritis mice was higher than the uninfected mice. Gastric DP T cells derived from lamina propria cells, which distributed in the gastric epithelial layer. We found that DP T cells exhibited anti-in ammatory function. In vitro, DP T cells inhibited the maturation of dendritic cells and the proliferation of CD4+ T cell. The elimination of CD4+CD8αα+ T cells in vivo resulted in severe gastritis and a reduction of H. felis load. Additionally, vaccine with silk broin as delivery systems enhanced vaccine e cacy by reducing DP T cells. We demonstrated that DP T cells performed an immunosuppressive role in Helicobacter felisinduced gastritis. These ndings revealed that DP T cells may affect the prognosis of the disease and the vaccine e cacy.

Animal Models and Helicobacter pylori Infection

“…al. demonstrated that CD4+ CD8αα+ double-positive intraepithelial T lymphocytes (DP T cells) play an immunosuppressive role in H. felis -induced gastritis, mediating chronic inflammation and possibly affecting disease prognosis [ 145 ]. Furthermore, a recent study has implicated the role of APRIL (a proliferation inducing ligand) in the development of gastric MALT lymphoma [ 146 ].…”