Limits...
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 in blood (PBMC) and gastric LPMC in children, adults, and the elderly. (A) PBMC and (B) gastric LPMC obtained from children (n = 12), adults (n = 21), and the elderly (n = 10) were evaluated for the presence of MAIT cells. Significant differences among age groups are denoted by asterisks (*P < 0.05). (C) Correlation of CD8+ MAIT cells with age in PBMC (n = 46) and (D) in gastric LPMC (n = 43) was performed using Spearman’s correlation analysis. Horizontal green lines in (A,B) represent medians.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4585133&req=5

Figure 2: MAIT cells in blood (PBMC) and gastric LPMC in children, adults, and the elderly. (A) PBMC and (B) gastric LPMC obtained from children (n = 12), adults (n = 21), and the elderly (n = 10) were evaluated for the presence of MAIT cells. Significant differences among age groups are denoted by asterisks (*P < 0.05). (C) Correlation of CD8+ MAIT cells with age in PBMC (n = 46) and (D) in gastric LPMC (n = 43) was performed using Spearman’s correlation analysis. Horizontal green lines in (A,B) represent medians.

Mentions: Because the presence of MAIT cells in the human gastric mucosa was not previously reported, we determined their frequency in gastric biopsies obtained from children, adults, and the elderly and compared these frequencies to blood MAIT cells. The frequencies of both MAIT cell subsets (CD8+ and DN) in blood were found to be significantly higher in children than in adults and the elderly (Figure 2A). In contrast, in LPMC, although some trends were noted, MAIT cell subsets frequencies were not different among the three age groups (Figure 2B). Using Pearson’s regression analysis, we observed a significant inverse correlation (r = −0.35, P = 0.016) between the frequency of the CD8+ MAIT subset and age in PBMC but not in LPMC (r = −0.03, P = 0.847) (Figures 2C,D). Regression analysis of DN subsets showed similar results, i.e., significant inverse correlations between the frequencies of blood DN (r = −0.33, P = 0.022) MAIT subsets and age (Figure S2A in Supplementary Material). Similar to LPMC CD8+ MAIT, DN MAIT subset showed a trend to be correlated (r = 0.25, P = 0.10) with age (Figure S2B in Supplementary Material).


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 in blood (PBMC) and gastric LPMC in children, adults, and the elderly. (A) PBMC and (B) gastric LPMC obtained from children (n = 12), adults (n = 21), and the elderly (n = 10) were evaluated for the presence of MAIT cells. Significant differences among age groups are denoted by asterisks (*P < 0.05). (C) Correlation of CD8+ MAIT cells with age in PBMC (n = 46) and (D) in gastric LPMC (n = 43) was performed using Spearman’s correlation analysis. Horizontal green lines in (A,B) represent medians.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4585133&req=5

Figure 2: MAIT cells in blood (PBMC) and gastric LPMC in children, adults, and the elderly. (A) PBMC and (B) gastric LPMC obtained from children (n = 12), adults (n = 21), and the elderly (n = 10) were evaluated for the presence of MAIT cells. Significant differences among age groups are denoted by asterisks (*P < 0.05). (C) Correlation of CD8+ MAIT cells with age in PBMC (n = 46) and (D) in gastric LPMC (n = 43) was performed using Spearman’s correlation analysis. Horizontal green lines in (A,B) represent medians.
Mentions: Because the presence of MAIT cells in the human gastric mucosa was not previously reported, we determined their frequency in gastric biopsies obtained from children, adults, and the elderly and compared these frequencies to blood MAIT cells. The frequencies of both MAIT cell subsets (CD8+ and DN) in blood were found to be significantly higher in children than in adults and the elderly (Figure 2A). In contrast, in LPMC, although some trends were noted, MAIT cell subsets frequencies were not different among the three age groups (Figure 2B). Using Pearson’s regression analysis, we observed a significant inverse correlation (r = −0.35, P = 0.016) between the frequency of the CD8+ MAIT subset and age in PBMC but not in LPMC (r = −0.03, P = 0.847) (Figures 2C,D). Regression analysis of DN subsets showed similar results, i.e., significant inverse correlations between the frequencies of blood DN (r = −0.33, P = 0.022) MAIT subsets and age (Figure S2A in Supplementary Material). Similar to LPMC CD8+ MAIT, DN MAIT subset showed a trend to be correlated (r = 0.25, P = 0.10) with age (Figure S2B in Supplementary Material).

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.