Mucosal-Associated Invariant T Cells in the Human Gastric Mucosa and Blood: Role in Helicobacter pylori Infection.
Mucosal-Associated Invariant T Cells in the Human Gastric Mucosa and Blood: Role in Helicobacter pylori Infection.
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DOI：
10.3389/fimmu.2015.00466
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发表时间：
2015
影响因子：
7.3
通讯作者：
Sztein MB
中科院分区：
文献类型：
--
作者：
Booth JS;Salerno-Goncalves R;Blanchard TG;Patil SA;Kader HA;Safta AM;Morningstar LM;Czinn SJ;Greenwald BD;Sztein MB
粘膜相关不变T（MAIT）细胞代表一类已在人血液、肝、肺和肠中表征的抗微生物先天性样T细胞。在这里，我们首次调查了接受常规内镜检查的儿童、成人和老年人胃中MAIT细胞的存在，并评估了它们对幽门螺杆菌（H.幽门螺杆菌- Hp），一种主要的胃病原体。我们观察到MAIT细胞存在于胃的固有层隔室中，并显示出与血液MAIT细胞相似的记忆表型。然后，我们证明了胃和血液MAIT细胞能够识别H。幽门。我们发现CD 8+和CD 4 − CD 8 −（双阴性）MAIT细胞亚群对H.幽门螺杆菌感染的巨噬细胞通过产生细胞因子（IFN-γ、TNF-α、IL-17 A）以MR-1限制性方式刺激并表现出细胞毒活性。有趣的是，我们观察到Hp+ve个体的血液MAIT细胞频率显著低于Hp−ve个体。然而，胃MAIT细胞频率在Hp+ve和Hp−ve个体之间没有显著差异，表明血液和胃组织之间存在二分法。此外，我们观察到大多数胃MAIT细胞（>80%）表达组织驻留标志物（CD 69 + CD 103+），其仅少量存在于PBMC MAIT细胞上（<3%），这表明胃MAIT细胞易于快速响应病原体。这些结果为了解MAIT细胞在外周和粘膜组织上的功能及其在宿主对H的反应中可能的影响提供了重要的新信息。幽门。
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.