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

Guojing Ruan,An Huang,Chupeng Hu,Ningyin Xu,Menghui Fan,Zhenxing Zhang,Yue Wang,Yingying Xing

doi:10.1016/j.micpath.2021.105151

Abstract

CD4+ CD8αα+ double-positive intraepithelial T lymphocytes (DP T cells), a newly characterized subset of intraepithelial T cells, are reported to contribute to local immunosuppression. However, the presence of DP T cells in Helicobacter. pylori -induced gastritis and their relationship with disease prognosis has yet to be elucidated. In this study, a chronic gastritis model was established by infecting mice with Helicobacter felis. Gastric-infiltrating lymphocytes were isolated from these mice and analyzed by flow cytometry. The frequency of DP T cells in H. felis-induced gastritis mice was higher than that in uninfected mice. The gastric DP T cells were derived from lamina propria cells but were predominantly distributed in the gastric epithelial layer. These gastric DP T cells also exhibited anti-inflammatory functions, and they inhibited the maturation of dendritic cells and proliferation of CD4+ T lymphocytes in vitro. Elimination of DP T cells simultaneously resulted in severe gastritis and a reduction of H. felis load in vivo. Finally, vaccine mixed with different adjuvants was used to explore the relationship between vaccine efficacy and DP cells. Silk fibroin as the vaccine delivery system enhanced vaccine efficacy by reducing the number of DP T cells. This study demonstrated that DP T cells perform an immunosuppressive role in Helicobacter felis-induced gastritis, and consequently, DP T cells may affect disease prognosis and vaccine efficacy.

Highlights

Helicobacter pylori (H. pylori) is a gram-negative, spiral- shaped and microaerophilic bacterium that colonizes in gastric mucosa of more than half of the world's population [9]
Liu. et al had demonstrated that the mice were vaccinated H. pylori vaccine in the gastric subserous layer (GSL) induced better protection against H. pylori infection.[12]we found that rather than other ways, vaccination in GSL induced a large number of CD4 + CD8αα + T cells
Our study showed that gastric CD4 + CD8αα + T cells were significantly increase in gastritis mice induced by H. felis

Summary

Introduction

Helicobacter pylori (H. pylori) is a gram-negative, spiral- shaped and microaerophilic bacterium that colonizes in gastric mucosa of more than half of the world's population [9] This bacterium is involved in several diseases such as chronic gastritis, gastric ulcer and gastric cancer [3, 17]. Studies show that DP IELs and Treg cells synergistically regulate intestinal inflammation [25] These studies show that CD4 + CD8αα + T cells are important subsets of CD4 + T lymphocytes in the intestinal epithelium and play an irreplaceable role in intestinal inflammation. The role of CD4 + CD8αα + T cells in gastritis is still not completely understood It is nothing is known about the effects of DP T cells in H. pylori persistent and vaccine efficacy

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