Human mucosal Vα7.2+CD161hi T cell distribution at physiologic state and inHelicobacter pyloriinfection

Abstract

Mucosal‐associated invariant T (MAIT) cells are innate‐like, unconventional T cells that are present in peripheral blood and mucosal surfaces. A clear understanding of how MAIT cells in the mucosae function and their role in host immunity is still lacking. Therefore, our aim was to investigate MAIT cell distribution and their characteristics in the gastrointestinal (GI) mucosal tissue based on Vα7.2+CD161hi identification. We showed that Vα7.2+CD161hi T cells are present in both intraepithelial layer and lamina propriae of the GI mucosa, but have different abundance at each GI site. Vα7.2+CD161hi T cells were most abundant in the duodenum, but had the lowest reactivity to MR1‐5‐OP‐RU tetramers when compared with Vα7.2+CD161hi T cells at other GI tissue sites. Striking discrepancies between MR1‐5‐OP‐RU tetramer reactive cells and Vα7.2+CD161hi T cells were observed along each GI tissue sites. Vα7.2+CD161hi TCR repertoire was most diverse in the ileum. Similar dominant profiles of TRBV usage were observed among peripheral blood, duodenum, ileum, and colon. Some TRBV chains were detected at certain intestinal sites and not elsewhere. The frequency of peripheral blood Vα7.2+CD161hi T cells correlated with mucosal Vα7.2+CD161hi T cells in lamina propriae ileum and lamina propriae colon. The frequency of peripheral blood Vα7.2+CD161hi T cells in Helicobacter pylori‐infected individuals was significantly lower than uninfected individuals, but this was not observed with gastric Vα7.2+CD161hi T cells. This study illustrates the biology of Vα7.2+CD161hi T cells in the GI mucosa and provides a basis for understanding MAIT cells in the mucosa and MAIT‐related GI diseases.

Mucosal-Associated Invariant T Cells in the Digestive System: Defender or Destroyer?

“…MAIT cells are widely distributed in the human body and are located in the liver, intestine, lungs, blood, skin, and female reproductive mucosa. 6 , 11 , 12 , 13 , 19 , 20 , 21 , 22 , 23 , 24 , 25 Nonhuman primates do not have as many MAIT cells as humans, but their distribution in the liver and mucosal tissues is similar to that of humans. 26 The frequency of MAIT cells in commonly used laboratory mice (C57BL/6J and BALB/c) is much lower than in humans.…”

Mucosal‐associated invariant T cells in digestive tract: Local guardians or destroyers?

“…MAIT cells are enriched in various types of tissues, accounting for 1%-10% of T cells in peripheral blood [24], 10% in the airway [33,34] and 20%-50% in the liver [24,35]. In stomach, MAIT accounts for about 1%-3% of all T cells in the gastric mucosa, and for the abundance in the gastric antrum is higher than that in the gastric body [36,37]. In the intestinal mucosa, MAIT accounts for up to 10% of αβT cells [24].…”

“…In the intestinal mucosa, MAIT accounts for up to 10% of αβT cells [24]. Furthermore, MAIT is highly enriched in the duodenum, but its reactivity towards the MR1-5-OP-RU tetramer is poor [36]. Another work has also shown that up to 25% of the TRAV1-2 + cells in the gastric mucosa cannot respond to the MR1-tetramer [27], addressing the importance of the MR1-tetramer in detecting tissue MAIT cells.…”

“…As described earlier, abundant groups of microbiomes exist in the gastrointestinal tract, which takes part in the regulation of MAIT development and function [61]. Thus, dysbiosis or infection may also result in abnormal MAIT activation and drive gastrointestinal inflammation, as reported in Vibrio cholerae O1 [62], H. pylori [27, 36, 48], M ycobacterium tuberculosis [63], Shigella flexneri [64], S. typhimurium [65] and so forth. Alongside dysbiosis, MAIT cells can migrate and redistribute to ectopic tissues to trigger local inflammation and even systemic inflammation [66].…”