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Mucosal-Associated Invariant T Cells in the Human Gastric Mucosa and Blood: Role in Helicobacter pylori Infection.

Booth JS, Salerno-Goncalves R, Blanchard TG, Patil SA, Kader HA, Safta AM, Morningstar LM, Czinn SJ, Greenwald BD, Sztein MB - Front Immunol (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


MAIT cells are lower in blood but not in the gastric mucosa of H. pylori-infected volunteers. Aggregate data of the percentages of MAIT cell subsets (CD8+ and CD4−CD8−) in H. pylori-negative (Hp−ve) (n = 20) and H. pylori-positive (Hp+ve) (n = 5) volunteers in (A) PBMC and (B) gastric LPMC. Hp−ve volunteers were age-matched to Hp+ve volunteers. (C) Representative example of tissue-resident T markers (CD69 and CD103) expression on CD8+ MAIT cells from PBMC and gastric LPMC. (D) Cumulative data (n = 6) comparing the expression of TR MAIT cells in PBMC and LPMC. Horizontal lines in (A,B,D) represent medians. Significant differences are denoted by asterisks (*P < 0.05, **P < 0.005).
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Figure 8: MAIT cells are lower in blood but not in the gastric mucosa of H. pylori-infected volunteers. Aggregate data of the percentages of MAIT cell subsets (CD8+ and CD4−CD8−) in H. pylori-negative (Hp−ve) (n = 20) and H. pylori-positive (Hp+ve) (n = 5) volunteers in (A) PBMC and (B) gastric LPMC. Hp−ve volunteers were age-matched to Hp+ve volunteers. (C) Representative example of tissue-resident T markers (CD69 and CD103) expression on CD8+ MAIT cells from PBMC and gastric LPMC. (D) Cumulative data (n = 6) comparing the expression of TR MAIT cells in PBMC and LPMC. Horizontal lines in (A,B,D) represent medians. Significant differences are denoted by asterisks (*P < 0.05, **P < 0.005).

Mentions: Because MAIT cells in both blood and gastric mucosa were found to be reactive to H. pylori-infected Mϕ, we speculated that there might be differences between MAIT cell frequencies between H. pylori-infected (Hp+ve) and uninfected (Hp−ve) volunteers. To explore this possibility, we assessed the frequency of MAIT cells in PBMC and gastric LPMC obtained from Hp+ve and Hp−ve volunteers. We observed significant decreases in the frequency of CD8+ MAIT cells in blood of Hp+ve compared with Hp−ve volunteers (Figure 8A). Analysis of the DN MAIT subsets revealed significant decreases in the frequencies of PBMC DN MAIT cells in Hp+ve when compared with Hp−ve volunteers (Figure 8A). These results indicated that decreased levels of CD8+ and DN MAIT cell subsets are present in blood during H. pylori infection. We then determined the frequency of MAIT cells in the gastric mucosa for the same Hp+ve and Hp−ve volunteers. Interestingly, no statistically significant differences were observed among the LPMC MAIT cell subset frequencies in gastric biopsies obtained from Hp+ve and Hp−ve groups (Figure 8B). Since our results suggest that MAIT cells in the gastric mucosa are relatively constant during aging and infection, we hypothesized that these gastric MAIT cells might represent populations of tissue-resident cells (TR). To explore this possibility, we assessed the hallmark markers of tissue-resident cells, i.e., expression of CD103 and CD69, on gastric LPMC and blood MAIT cells. We observed that TR cells (i.e., CD103+ CD69+) represented the majority of MAIT cells in gastric LPMC, but only a small proportion in PBMC (Figures 8C,D).


Mucosal-Associated Invariant T Cells in the Human Gastric Mucosa and Blood: Role in Helicobacter pylori Infection.

Booth JS, Salerno-Goncalves R, Blanchard TG, Patil SA, Kader HA, Safta AM, Morningstar LM, Czinn SJ, Greenwald BD, Sztein MB - Front Immunol (2015)

MAIT cells are lower in blood but not in the gastric mucosa of H. pylori-infected volunteers. Aggregate data of the percentages of MAIT cell subsets (CD8+ and CD4−CD8−) in H. pylori-negative (Hp−ve) (n = 20) and H. pylori-positive (Hp+ve) (n = 5) volunteers in (A) PBMC and (B) gastric LPMC. Hp−ve volunteers were age-matched to Hp+ve volunteers. (C) Representative example of tissue-resident T markers (CD69 and CD103) expression on CD8+ MAIT cells from PBMC and gastric LPMC. (D) Cumulative data (n = 6) comparing the expression of TR MAIT cells in PBMC and LPMC. Horizontal lines in (A,B,D) represent medians. Significant differences are denoted by asterisks (*P < 0.05, **P < 0.005).
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Figure 8: MAIT cells are lower in blood but not in the gastric mucosa of H. pylori-infected volunteers. Aggregate data of the percentages of MAIT cell subsets (CD8+ and CD4−CD8−) in H. pylori-negative (Hp−ve) (n = 20) and H. pylori-positive (Hp+ve) (n = 5) volunteers in (A) PBMC and (B) gastric LPMC. Hp−ve volunteers were age-matched to Hp+ve volunteers. (C) Representative example of tissue-resident T markers (CD69 and CD103) expression on CD8+ MAIT cells from PBMC and gastric LPMC. (D) Cumulative data (n = 6) comparing the expression of TR MAIT cells in PBMC and LPMC. Horizontal lines in (A,B,D) represent medians. Significant differences are denoted by asterisks (*P < 0.05, **P < 0.005).
Mentions: Because MAIT cells in both blood and gastric mucosa were found to be reactive to H. pylori-infected Mϕ, we speculated that there might be differences between MAIT cell frequencies between H. pylori-infected (Hp+ve) and uninfected (Hp−ve) volunteers. To explore this possibility, we assessed the frequency of MAIT cells in PBMC and gastric LPMC obtained from Hp+ve and Hp−ve volunteers. We observed significant decreases in the frequency of CD8+ MAIT cells in blood of Hp+ve compared with Hp−ve volunteers (Figure 8A). Analysis of the DN MAIT subsets revealed significant decreases in the frequencies of PBMC DN MAIT cells in Hp+ve when compared with Hp−ve volunteers (Figure 8A). These results indicated that decreased levels of CD8+ and DN MAIT cell subsets are present in blood during H. pylori infection. We then determined the frequency of MAIT cells in the gastric mucosa for the same Hp+ve and Hp−ve volunteers. Interestingly, no statistically significant differences were observed among the LPMC MAIT cell subset frequencies in gastric biopsies obtained from Hp+ve and Hp−ve groups (Figure 8B). Since our results suggest that MAIT cells in the gastric mucosa are relatively constant during aging and infection, we hypothesized that these gastric MAIT cells might represent populations of tissue-resident cells (TR). To explore this possibility, we assessed the hallmark markers of tissue-resident cells, i.e., expression of CD103 and CD69, on gastric LPMC and blood MAIT cells. We observed that TR cells (i.e., CD103+ CD69+) represented the majority of MAIT cells in gastric LPMC, but only a small proportion in PBMC (Figures 8C,D).

Bottom Line: 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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.