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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.


Responses of blood CD4−CD8− (DN) MAIT subsets from healthy adults to H. pylori-infected macrophages. (A) Representative volunteer showing the induction of cytokine production (IFN-γ, TNF-α, IL-17A) and up-regulation of CD107a expression in DN MAIT cells following stimulation with media (alone), non-infected THP-1 macrophages (Mϕ), or H. pylori-infected THP-1 Mϕ (E:T – 50:1). (B) Cumulative data (n = 11) showing production of cytokines (IFN-γ, TNF-α, and IL-17A) and expression of CD107a by DN MAIT cells following stimulation with H. pylori-infected THP-1 Mϕ (E:T – 50:1). (C) CD69 up-regulation by CD3+CD161+TCR Vα7.2+ cells following H. pylori-infected THP-1 Mϕ stimulation (E:T – 50:1) and assessment of the level of cytokines production (IFN-γ, TNF-α, IL-17A) and CD107a expression in CD69+ MAIT cell subsets (CD8+ and CD4−CD8−) following stimulation with H. pylori-infected THP-1 Mϕ (E:T – 50:1) (n = 11). Horizontal black lines in (B,C) represent medians. Significant differences are denoted by asterisks (**P < 0.005).
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Figure 4: Responses of blood CD4−CD8− (DN) MAIT subsets from healthy adults to H. pylori-infected macrophages. (A) Representative volunteer showing the induction of cytokine production (IFN-γ, TNF-α, IL-17A) and up-regulation of CD107a expression in DN MAIT cells following stimulation with media (alone), non-infected THP-1 macrophages (Mϕ), or H. pylori-infected THP-1 Mϕ (E:T – 50:1). (B) Cumulative data (n = 11) showing production of cytokines (IFN-γ, TNF-α, and IL-17A) and expression of CD107a by DN MAIT cells following stimulation with H. pylori-infected THP-1 Mϕ (E:T – 50:1). (C) CD69 up-regulation by CD3+CD161+TCR Vα7.2+ cells following H. pylori-infected THP-1 Mϕ stimulation (E:T – 50:1) and assessment of the level of cytokines production (IFN-γ, TNF-α, IL-17A) and CD107a expression in CD69+ MAIT cell subsets (CD8+ and CD4−CD8−) following stimulation with H. pylori-infected THP-1 Mϕ (E:T – 50:1) (n = 11). Horizontal black lines in (B,C) represent medians. Significant differences are denoted by asterisks (**P < 0.005).

Mentions: We observed that higher percentages of DN MAIT cells produced cytokines (IFN-γ, TNF-α, and IL-17A) and up-regulated CD107a expression following stimulation with H. pylori-infected THP-1 Mϕ (E:T – 50:1) than when exposed to non-infected Mϕ or when effector cells were cultured alone (Figure 4A). Cumulative data (n = 11) showed that significantly higher percentages of DN MAIT cells produced cytokines (IFN-γ, IL-17, and TNF-α) and up-regulated CD107a following stimulation with H. pylori-infected Mϕ than with non-infected Mϕ (Figure 4B).


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)

Responses of blood CD4−CD8− (DN) MAIT subsets from healthy adults to H. pylori-infected macrophages. (A) Representative volunteer showing the induction of cytokine production (IFN-γ, TNF-α, IL-17A) and up-regulation of CD107a expression in DN MAIT cells following stimulation with media (alone), non-infected THP-1 macrophages (Mϕ), or H. pylori-infected THP-1 Mϕ (E:T – 50:1). (B) Cumulative data (n = 11) showing production of cytokines (IFN-γ, TNF-α, and IL-17A) and expression of CD107a by DN MAIT cells following stimulation with H. pylori-infected THP-1 Mϕ (E:T – 50:1). (C) CD69 up-regulation by CD3+CD161+TCR Vα7.2+ cells following H. pylori-infected THP-1 Mϕ stimulation (E:T – 50:1) and assessment of the level of cytokines production (IFN-γ, TNF-α, IL-17A) and CD107a expression in CD69+ MAIT cell subsets (CD8+ and CD4−CD8−) following stimulation with H. pylori-infected THP-1 Mϕ (E:T – 50:1) (n = 11). Horizontal black lines in (B,C) represent medians. Significant differences are denoted by asterisks (**P < 0.005).
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Figure 4: Responses of blood CD4−CD8− (DN) MAIT subsets from healthy adults to H. pylori-infected macrophages. (A) Representative volunteer showing the induction of cytokine production (IFN-γ, TNF-α, IL-17A) and up-regulation of CD107a expression in DN MAIT cells following stimulation with media (alone), non-infected THP-1 macrophages (Mϕ), or H. pylori-infected THP-1 Mϕ (E:T – 50:1). (B) Cumulative data (n = 11) showing production of cytokines (IFN-γ, TNF-α, and IL-17A) and expression of CD107a by DN MAIT cells following stimulation with H. pylori-infected THP-1 Mϕ (E:T – 50:1). (C) CD69 up-regulation by CD3+CD161+TCR Vα7.2+ cells following H. pylori-infected THP-1 Mϕ stimulation (E:T – 50:1) and assessment of the level of cytokines production (IFN-γ, TNF-α, IL-17A) and CD107a expression in CD69+ MAIT cell subsets (CD8+ and CD4−CD8−) following stimulation with H. pylori-infected THP-1 Mϕ (E:T – 50:1) (n = 11). Horizontal black lines in (B,C) represent medians. Significant differences are denoted by asterisks (**P < 0.005).
Mentions: We observed that higher percentages of DN MAIT cells produced cytokines (IFN-γ, TNF-α, and IL-17A) and up-regulated CD107a expression following stimulation with H. pylori-infected THP-1 Mϕ (E:T – 50:1) than when exposed to non-infected Mϕ or when effector cells were cultured alone (Figure 4A). Cumulative data (n = 11) showed that significantly higher percentages of DN MAIT cells produced cytokines (IFN-γ, IL-17, and TNF-α) and up-regulated CD107a following stimulation with H. pylori-infected Mϕ than with non-infected Mϕ (Figure 4B).

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.