title: Mucosal-Associated Invariant T Cells in the Human Gastric Mucosa and Blood: Role in Helicobacter pylori Infection.
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.
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine , Baltimore, MD , USA ; Department of Pediatrics, University of Maryland School of Medicine , Baltimore, MD , USA.
authors.forename: Jayaum S
authors.initials: JS
authors.lastname: Booth
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine , Baltimore, MD , USA ; Department of Pediatrics, University of Maryland School of Medicine , Baltimore, MD , USA.
authors.forename: Rosangela
authors.initials: R
authors.lastname: Salerno-Goncalves
authors.affiliation: Department of Pediatrics, University of Maryland School of Medicine , Baltimore, MD , USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Blanchard
authors.affiliation: Department of Medicine, University of Maryland School of Medicine , Baltimore, MD , USA ; Division of Gastroenterology and Hepatology, University of Maryland School of Medicine , Baltimore, MD , USA.
authors.forename: Seema A
authors.initials: SA
authors.lastname: Patil
authors.affiliation: Department of Pediatrics, University of Maryland School of Medicine , Baltimore, MD , USA.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Kader
authors.affiliation: Department of Pediatrics, University of Maryland School of Medicine , Baltimore, MD , USA.
authors.forename: Anca M
authors.initials: AM
authors.lastname: Safta
authors.affiliation: Department of Pediatrics, University of Maryland School of Medicine , Baltimore, MD , USA.
authors.forename: Lindsay M
authors.initials: LM
authors.lastname: Morningstar
authors.affiliation: Department of Pediatrics, University of Maryland School of Medicine , Baltimore, MD , USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Czinn
authors.affiliation: Department of Medicine, University of Maryland School of Medicine , Baltimore, MD , USA ; Division of Gastroenterology and Hepatology, University of Maryland School of Medicine , Baltimore, MD , USA.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Greenwald
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine , Baltimore, MD , USA ; Department of Pediatrics, University of Maryland School of Medicine , Baltimore, MD , USA ; Department of Medicine, University of Maryland School of Medicine , Baltimore, MD , USA.
authors.forename: Marcelo B
authors.initials: MB
authors.lastname: Sztein
keywords: H. pylori; age-related; cytotoxic; gastric MAIT; stomach