Human mucosal associated invariant T cells detect bacterially infected cells.
Human mucosal associated invariant T cells detect bacterially infected cells.
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DOI：
10.1371/journal.pbio.1000407
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发表时间：
2010-06-29
期刊：
影响因子：
9.8
通讯作者：
Lewinsohn DM
中科院分区：
文献类型：
--
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
粘膜相关不变T（MAIT）细胞的生物学作用的第一个迹象表明，这种离散的T细胞亚群对细菌感染具有广泛的反应性。特别是MAIT细胞通过进化上最保守的主要组织相容性分子识别结核分枝杆菌感染的肺气道上皮细胞。控制结核分枝杆菌（Mtb）感染需要Th 1型免疫，其中CD 8 + T细胞发挥独特的作用。高频率Mtb反应性CD 8 + T细胞存在于Mtb感染和未感染的人中。我们通过有限稀释分析表明，非经典限制性CD 8 + T细胞是普遍存在的，但占主导地位的结核分枝杆菌未感染的个人。有趣的是，这些Mtb反应性细胞表达Vα7.2 T细胞受体（TCR），受非经典MHC（HLA-Ib）分子MR 1的限制，并以与抗原加工和呈递（TAP）无关的方式激活。这些特性都是粘膜相关不变T细胞（MAIT）的特征，MAIT是一种功能未知的“先天”T细胞群。这些MAIT细胞也检测被其他细菌感染的细胞。直接离体分析表明，Mtb反应性MAIT细胞减少外周血单核细胞（PBMC）从个人活动性结核病，富集在人肺，并响应Mtb感染的MR 1表达肺上皮细胞。总的来说，这些发现表明MAIT细胞在检测细菌感染的细胞中的普遍作用，并可能在控制细菌感染中发挥作用。世界上大约三分之一的人口感染了结核杆菌（Mtb），但由于强大的免疫反应，大多数感染者保持健康。CD 8 T细胞在检测细胞内感染方面是独特的。令人惊讶的是，Mtb反应性CD 8 T细胞在先前未暴露于Mtb的人中发现。我们表明，粘膜相关的不变T（MAIT）细胞，这没有以前已知的体内功能，弥补了这些结核分枝杆菌反应性CD 8 T细胞的比例和检测结核分枝杆菌感染的细胞通过一个特定的主要组织相容性分子称为MHC相关分子1，这是进化保守的哺乳动物。Mtb反应性MAIT细胞在肺中富集，并检测来自气道的原发性Mtb感染的肺上皮细胞，在气道中发生初始暴露于Mtb。我们继续表明，MAIT细胞对Mtb没有特异性，因为它们可以检测被各种其他细菌感染的细胞。奇怪的是，活动性结核病患者的血液中不存在Mtb反应性MAIT细胞。我们假设MAIT细胞是细菌感染的先天检测器，准备在控制细胞内感染中发挥作用。
A first indication of the biological role of mucosal associated invariant T (MAIT) cells reveals that this discrete T cell subset is broadly reactive to bacterial infection. In particular MAIT cells recognize Mycobacterium tuberculosis-infected lung airway epithelial cells via the most evolutionarily conserved major histocompatibility molecule. Control of infection with Mycobacterium tuberculosis (Mtb) requires Th1-type immunity, of which CD8+ T cells play a unique role. High frequency Mtb-reactive CD8+ T cells are present in both Mtb-infected and uninfected humans. We show by limiting dilution analysis that nonclassically restricted CD8+ T cells are universally present, but predominate in Mtb-uninfected individuals. Interestingly, these Mtb-reactive cells expressed the Vα7.2 T-cell receptor (TCR), were restricted by the nonclassical MHC (HLA-Ib) molecule MR1, and were activated in a transporter associated with antigen processing and presentation (TAP) independent manner. These properties are all characteristics of mucosal associated invariant T cells (MAIT), an “innate” T-cell population of previously unknown function. These MAIT cells also detect cells infected with other bacteria. Direct ex vivo analysis demonstrates that Mtb-reactive MAIT cells are decreased in peripheral blood mononuclear cells (PBMCs) from individuals with active tuberculosis, are enriched in human lung, and respond to Mtb-infected MR1-expressing lung epithelial cells. Overall, these findings suggest a generalized role for MAIT cells in the detection of bacterially infected cells, and potentially in the control of bacterial infection. About one-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), yet thanks to a robust immune response most infected people remain healthy. CD8 T cells are unique in detecting intracellular infections. Surprisingly, Mtb-reactive CD8 T cells are found in humans with no prior exposure to Mtb. We show that mucosal associated invariant T (MAIT) cells, which have no previously known in vivo function, make up a proportion of these Mtb-reactive CD8 T cells and detect Mtb-infected cells via a specific major histocompatibility molecule called MHC-related molecule 1, which is evolutionarily conserved among mammals. Mtb-reactive MAIT cells are enriched in lung and detect primary Mtb-infected lung epithelial cells from the airway where initial exposure to Mtb occurs. We go on to show that MAIT cells are not specific for Mtb since they can detect cells infected with a variety of other bacteria. Curiously, Mtb-reactive MAIT cells are absent in the blood of individuals with active tuberculosis. We postulate that MAIT cells are innate detectors of bacterial infection poised to play a role in control of intracellular infection.
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影响因子：
56.9
作者：
HASHIMOTO, K;HIRAI, M;KUROSAWA, Y
通讯作者：
KUROSAWA, Y
影响因子：
6.7
作者：
Lewinsohn, Deborah A;Winata, Ervina;Swarbrick, Gwendolyn M;Tanner, Katie E;Cook, Matthew S;Null, Megan D;Cansler, Meghan E;Sette, Alessandro;Sidney, John;Lewinsohn, David M
通讯作者：
Lewinsohn, David M
MTB衍生的抗原对人CD8+ T细胞的HLA-E依赖性表现。
影响因子：
15.3
作者：
Heinzel, Amy S;Grotzke, Jeff E;Lines, Rebecca A;Lewinsohn, Deborah A;McNabb, Andria L;Streblow, Daniel N;Braud, Veronique M;Grieser, Heather J;Belisle, John T;Lewinsohn, David M
通讯作者：
Lewinsohn, David M
影响因子：
3.2
作者：
HIRSCHFIELD, GR;MCNEIL, M;BRENNAN, PJ
通讯作者：
BRENNAN, PJ
影响因子：
15.3
作者：
DELIBERO, G;CASORATI, G;LANZAVECCHIA, A
通讯作者：
LANZAVECCHIA, A