Abstract
Mucosal-associated invariant T (MAIT) cells represent a class of antimicrobial innate-like T cells that have been characterized in human blood, liver, lungs, and intestine. Here, we investigated, for the first time, the presence of MAIT cells in the stomach of children, adults, and the elderly undergoing routine endoscopy and assessed their reactivity to Helicobacter pylori (H. pylori – Hp), a major gastric pathogen. We observed that MAIT cells are present in the lamina propria compartment of the stomach and display a similar memory phenotype to blood MAIT cells. We then demonstrated that gastric and blood MAIT cells are able to recognize H. pylori. We found that CD8+ and CD4−CD8− (double negative) MAIT cell subsets respond to H. pylori-infected macrophages stimulation in a MR-1 restrictive manner by producing cytokines (IFN-γ, TNF-α, IL-17A) and exhibiting cytotoxic activity. Interestingly, we observed that blood MAIT cell frequency in Hp+ve individuals was significantly lower than in Hp−ve individuals. However, gastric MAIT cell frequency was not significantly different between Hp+ve and Hp−ve individuals, demonstrating a dichotomy between blood and gastric tissues. Further, we observed that the majority of gastric MAIT cells (>80%) expressed tissue-resident markers (CD69+ CD103+), which were only marginally present on PBMC MAIT cells (<3%), suggesting that gastric MAIT cells are readily available to respond quickly to pathogens. These results contribute important new information to the understanding of MAIT cells function on peripheral and mucosal tissues and its possible implications in the host response to H. pylori.
Highlights
Innate T cells are distinct from conventional T cells in that they have a limited repertoire diversity and that their responses display innate-like properties [1]
To evaluate whether Mucosal-associated invariant T (MAIT) cells are present in the human stomach, we isolated LP mononuclear cells (LPMCs) from gastric biopsies obtained from various age groups and characterized them by flow cytometry
Cumulative data showed that the percentages of gastric CD8+ and DN MAIT cell subsets were significantly lower than their counterpart MAIT subsets in blood (Figure 1C)
Summary
Innate T cells are distinct from conventional T cells in that they have a limited repertoire diversity and that their responses display innate-like properties [1]. Three subsets of innate T cells have been implicated in detection and response to pathogens, i.e., natural killer T cells (NKT), gamma-delta (γδ) T cells, and mucosal-associated invariant T (MAIT) cells [2,3,4]. NKT and γδ T cells have been characterized in the gastric mucosa [8, 9], the presence of MAIT cells has not been reported. We have previously shown that gastric LP mononuclear cells (LPMCs) obtained from healthy volunteers contained more CD8+ T cells than CD4+ T cells, making the presence of CD8+ MAIT cells in the gastric milieu a distinct possibility [10]
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