MAIT cells are licensed through granzyme exchange to kill bacterially sensitized targets.
MAIT cells are licensed through granzyme exchange to kill bacterially sensitized targets.
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粘膜相关不变性T细胞（MAIT）是一种先天样T细胞群，受非多态性、主要组织相容性复合体i类相关蛋白1 （MR1）的限制。通过检测MR1结合的核黄素代谢物，MAIT细胞被广泛的细菌激活，但它们在识别同源靶细胞时的直接细胞溶解能力尚不清楚。我们发现，静止的人MAIT细胞具有独特的特征，缺乏颗粒酶（Gr） B和低穿孔蛋白表达，穿孔蛋白是有效细胞毒性活性所需的关键颗粒蛋白，但GrA和GrK的表达水平很高。细菌激活的MAIT细胞迅速诱导GrB和穿孔素，使这些细胞能够杀死它们的同源靶细胞。使用一种新的基于流式细胞术的杀伤实验，我们发现许可的MAIT细胞，而不是来自同一供体的离体MAIT细胞，可以以MR1和脱颗粒依赖的方式有效地杀死暴露于大肠杆菌的b细胞系。最后，我们发现MAIT细胞在抗原和细胞因子刺激下具有高度增殖，保持GrB、穿孔素和GrA的高表达，但在抗原增殖后GrK的表达降低。严格调节MAIT细胞的细胞溶解能力可能在控制细胞内细菌感染（如结核分枝杆菌）中发挥重要作用。
Mucosal-associated invariant T (MAIT) cells are an innate-like T-cell population restricted by the non-polymorphic, major histocompatibility complex class I-related protein 1, MR1. MAIT cells are activated by a broad range of bacteria through detection of riboflavin metabolites bound by MR1, but their direct cytolytic capacity upon recognition of cognate target cells remains unclear. We show that resting human MAIT cells are uniquely characterized by a lack of granzyme (Gr) B and low perforin expression, key granule proteins required for efficient cytotoxic activity, but high levels of expression of GrA and GrK. Bacterial activation of MAIT cells rapidly induced GrB and perforin, licensing these cells to kill their cognate target cells. Using a novel flow cytometry-based killing assay, we show that licensed MAIT cells, but not ex vivo MAIT cells from the same donors, can efficiently kill Escherichia coli-exposed B-cell lines in an MR1- and degranulation-dependent manner. Finally, we show that MAIT cells are highly proliferative in response to antigenic and cytokine stimulation, maintaining high expression of GrB, perforin, and GrA, but reduced expression of GrK following antigenic proliferation. The tightly regulated cytolytic capacity of MAIT cells may have an important role in the control of intracellular bacterial infections, such as Mycobacterium tuberculosis.
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影响因子：
30.5
作者：
Le Bourhis, Lionel;Martin, Emmanuel;Lantz, Olivier
通讯作者：
Lantz, Olivier
影响因子：
3.7
作者：
Cooper DM;Pechkovsky DV;Hackett TL;Knight DA;Granville DJ
通讯作者：
Granville DJ
影响因子：
6.7
作者：
Le Bourhis L;Dusseaux M;Bohineust A;Bessoles S;Martin E;Premel V;Coré M;Sleurs D;Serriari NE;Treiner E;Hivroz C;Sansonetti P;Gougeon ML;Soudais C;Lantz O
通讯作者：
Lantz O
DOI：
10.4049/jimmunol.1100789
发表时间：
2011-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jiang W;Chai NR;Maric D;Bielekova B
通讯作者：
Bielekova B
影响因子：
9.8
作者：
Gold MC;Cerri S;Smyk-Pearson S;Cansler ME;Vogt TM;Delepine J;Winata E;Swarbrick GM;Chua WJ;Yu YY;Lantz O;Cook MS;Null MD;Jacoby DB;Harriff MJ;Lewinsohn DA;Hansen TH;Lewinsohn DM
通讯作者：
Lewinsohn DM