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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 present in the human gastric mucosa and exhibit T effector memory phenotype. (A) Identification of MAIT cell subsets [CD8+, CD4+, and CD4−CD8− (DN)] in PBMC and (B) in gastric LPMC in a representative individual as CD161hi TCR Vα7.2 (box). (C) Comparison of gastric (red dots; n = 27) and PBMC (black squares; n = 29) MAIT cell subsets. Significant differences between MAIT cell subsets in (i) PBMC [black asterisks (*)] and (ii) gastric LPMC [red asterisk (*)]. Blue asterisks (*) denote significant differences in MAIT cell subsets between PBMC and LPMC. Horizontal lines represent medians (red bars: gastric MAIT; black bars: PBMC MAIT). (D) Expression of CD45RA and CD62L to evaluate memory [TCM (CD62L+CD45RA−), TEM (CD62L−CD45RA−), and TEMRA (CD62L−CD45RA+)] and Tnaive (CD62L+CD45RA+) subpopulations in MAIT subsets from PBMC (n = 29) and (E) LPMC (n = 27). (F) Comparison of TEM MAIT cell subsets between PBMC and LPMC. *P < 0.05; **P < 0.005; ***P < 0.0005.
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Figure 1: MAIT cells are present in the human gastric mucosa and exhibit T effector memory phenotype. (A) Identification of MAIT cell subsets [CD8+, CD4+, and CD4−CD8− (DN)] in PBMC and (B) in gastric LPMC in a representative individual as CD161hi TCR Vα7.2 (box). (C) Comparison of gastric (red dots; n = 27) and PBMC (black squares; n = 29) MAIT cell subsets. Significant differences between MAIT cell subsets in (i) PBMC [black asterisks (*)] and (ii) gastric LPMC [red asterisk (*)]. Blue asterisks (*) denote significant differences in MAIT cell subsets between PBMC and LPMC. Horizontal lines represent medians (red bars: gastric MAIT; black bars: PBMC MAIT). (D) Expression of CD45RA and CD62L to evaluate memory [TCM (CD62L+CD45RA−), TEM (CD62L−CD45RA−), and TEMRA (CD62L−CD45RA+)] and Tnaive (CD62L+CD45RA+) subpopulations in MAIT subsets from PBMC (n = 29) and (E) LPMC (n = 27). (F) Comparison of TEM MAIT cell subsets between PBMC and LPMC. *P < 0.05; **P < 0.005; ***P < 0.0005.

Mentions: To evaluate whether MAIT cells are present in the human stomach, we isolated LPMCs from gastric biopsies obtained from various age groups and characterized them by flow cytometry. We then compared the phenotype and function of MAIT cells present in the stomach with those present in the blood. As expected, blood MAIT cells were detected in the three major T-cell subsets CD8+, CD4+, and CD4−CD8− (DN) (Figure 1A; Figure S1 in Supplementary Material). Although at different proportions, gastric MAIT cells were also composed of three different subsets: CD8+, CD4+, and DN MAIT cell subsets (Figure 1B; Figure S1 in Supplementary Material). 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). In addition, the percentages of blood and gastric CD8+ and DN MAIT cell subsets were significantly higher than CD4+ MAIT subsets (Figure 1C).


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 present in the human gastric mucosa and exhibit T effector memory phenotype. (A) Identification of MAIT cell subsets [CD8+, CD4+, and CD4−CD8− (DN)] in PBMC and (B) in gastric LPMC in a representative individual as CD161hi TCR Vα7.2 (box). (C) Comparison of gastric (red dots; n = 27) and PBMC (black squares; n = 29) MAIT cell subsets. Significant differences between MAIT cell subsets in (i) PBMC [black asterisks (*)] and (ii) gastric LPMC [red asterisk (*)]. Blue asterisks (*) denote significant differences in MAIT cell subsets between PBMC and LPMC. Horizontal lines represent medians (red bars: gastric MAIT; black bars: PBMC MAIT). (D) Expression of CD45RA and CD62L to evaluate memory [TCM (CD62L+CD45RA−), TEM (CD62L−CD45RA−), and TEMRA (CD62L−CD45RA+)] and Tnaive (CD62L+CD45RA+) subpopulations in MAIT subsets from PBMC (n = 29) and (E) LPMC (n = 27). (F) Comparison of TEM MAIT cell subsets between PBMC and LPMC. *P < 0.05; **P < 0.005; ***P < 0.0005.
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Figure 1: MAIT cells are present in the human gastric mucosa and exhibit T effector memory phenotype. (A) Identification of MAIT cell subsets [CD8+, CD4+, and CD4−CD8− (DN)] in PBMC and (B) in gastric LPMC in a representative individual as CD161hi TCR Vα7.2 (box). (C) Comparison of gastric (red dots; n = 27) and PBMC (black squares; n = 29) MAIT cell subsets. Significant differences between MAIT cell subsets in (i) PBMC [black asterisks (*)] and (ii) gastric LPMC [red asterisk (*)]. Blue asterisks (*) denote significant differences in MAIT cell subsets between PBMC and LPMC. Horizontal lines represent medians (red bars: gastric MAIT; black bars: PBMC MAIT). (D) Expression of CD45RA and CD62L to evaluate memory [TCM (CD62L+CD45RA−), TEM (CD62L−CD45RA−), and TEMRA (CD62L−CD45RA+)] and Tnaive (CD62L+CD45RA+) subpopulations in MAIT subsets from PBMC (n = 29) and (E) LPMC (n = 27). (F) Comparison of TEM MAIT cell subsets between PBMC and LPMC. *P < 0.05; **P < 0.005; ***P < 0.0005.
Mentions: To evaluate whether MAIT cells are present in the human stomach, we isolated LPMCs from gastric biopsies obtained from various age groups and characterized them by flow cytometry. We then compared the phenotype and function of MAIT cells present in the stomach with those present in the blood. As expected, blood MAIT cells were detected in the three major T-cell subsets CD8+, CD4+, and CD4−CD8− (DN) (Figure 1A; Figure S1 in Supplementary Material). Although at different proportions, gastric MAIT cells were also composed of three different subsets: CD8+, CD4+, and DN MAIT cell subsets (Figure 1B; Figure S1 in Supplementary Material). 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). In addition, the percentages of blood and gastric CD8+ and DN MAIT cell subsets were significantly higher than CD4+ MAIT subsets (Figure 1C).

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.