Postnatal Expansion, Maturation, and Functionality of MR1T Cells in Humans.
Postnatal Expansion, Maturation, and Functionality of MR1T Cells in Humans.
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DOI：
10.3389/fimmu.2020.556695
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发表时间：
2020
影响因子：
7.3
通讯作者：
Lewinsohn DA
中科院分区：
文献类型：
--
作者：
Swarbrick GM;Gela A;Cansler ME;Null MD;Duncan RB;Nemes E;Shey M;Nsereko M;Mayanja-Kizza H;Kiguli S;Koh J;Hanekom WA;Hatherill M;Lancioni C;Lewinsohn DM;Scriba TJ;Lewinsohn DA
MR1 限制性 T (MR1T) 细胞的定义是其识别由单态 MHC 1 类相关分子 MR1 呈递的代谢抗原，MR1 是哺乳动物物种中最高度保守的 MHC I 类相关分子。粘膜相关不变 T (MAIT) 细胞是表达不变 TCR α 链 TRAV1-2 的 MR1T 细胞的主要子集。这些细胞包含一个 T 细胞子集，可识别并介导宿主对多种微生物病原体（包括结核分枝杆菌）的免疫反应。在这里，我们试图表征循环人类 MR1T 细胞（由 MR1-5-OP-RU 四聚体标记定义）和 TRAV1-2+ MAIT 细胞（由 TRAV1-2 表达和 CD26 和 CD161 高表达（TRAV1-2+CD161++CD26++ 细胞）定义）的发育。我们分析了来自三个不同地理环境、不同结核病 (TB) 疫苗接种实践、结核分枝杆菌暴露和感染水平的队列中外周血 MR1-5-OP-RU 四聚体 + MR1T 细胞的出生后扩增、成熟和功能。出生后早期，MR1-5-OP-RU 四聚体+ MR1T 细胞的频率迅速增加数倍。这与新生儿中以 CD4+ 和 TRAV1-2− 为主的群体向以 TRAV1-2+CD161++CD26++ CD8+ 群体为主的转变相一致。我们还观察到，在分枝杆菌刺激下表达 TNF 的四聚体+ MR1T 细胞在新生儿中非常低，但在生命第一年增加了约 10 倍。所有年龄组中的这些功能性 MR1T 细胞均为 MR1-5-OP-RU 四聚体 + TRAV1-2+ 和高表达的 CD161 和 CD26，这些标记物似乎表明该细胞亚群的表型和功能成熟。这种与年龄相关的成熟还表现为四聚体+ TRAV1-2+ MR1T 细胞上幼稚 T 细胞标记物的丢失比四聚体+ TRAV1-2− MR1T 细胞和非 MR1T 细胞更快。这些数据表明，新生儿具有罕见的具有不同表型属性的 MR1T 细胞群。并且暴露于环境会快速且优先地扩增 MR1T 细胞的 MR1-5-OP-RU 四聚体+TRAV1-2+ 群体，这些细胞成为儿童早期功能性 MR1T 细胞的主要群体。
MR1-restricted T (MR1T) cells are defined by their recognition of metabolite antigens presented by the monomorphic MHC class 1-related molecule, MR1, the most highly conserved MHC class I related molecule in mammalian species. Mucosal-associated invariant T (MAIT) cells are the predominant subset of MR1T cells expressing an invariant TCR α-chain, TRAV1-2. These cells comprise a T cell subset that recognizes and mediates host immune responses to a broad array of microbial pathogens, including Mycobacterium tuberculosis. Here, we sought to characterize development of circulating human MR1T cells as defined by MR1-5-OP-RU tetramer labeling and of the TRAV1-2+ MAIT cells defined by expression of TRAV1-2 and high expression of CD26 and CD161 (TRAV1-2+CD161++CD26++ cells). We analyzed postnatal expansion, maturation, and functionality of peripheral blood MR1-5-OP-RU tetramer+ MR1T cells in cohorts from three different geographic settings with different tuberculosis (TB) vaccination practices, levels of exposure to and infection with M. tuberculosis. Early after birth, frequencies of MR1-5-OP-RU tetramer+ MR1T cells increased rapidly by several fold. This coincided with the transition from a predominantly CD4+ and TRAV1-2− population in neonates, to a predominantly TRAV1-2+CD161++CD26++ CD8+ population. We also observed that tetramer+ MR1T cells that expressed TNF upon mycobacterial stimulation were very low in neonates, but increased ~10-fold in the first year of life. These functional MR1T cells in all age groups were MR1-5-OP-RU tetramer+TRAV1-2+ and highly expressed CD161 and CD26, markers that appeared to signal phenotypic and functional maturation of this cell subset. This age-associated maturation was also marked by the loss of naïve T cell markers on tetramer+ TRAV1-2+ MR1T cells more rapidly than tetramer+TRAV1-2− MR1T cells and non-MR1T cells. These data suggest that neonates have infrequent populations of MR1T cells with diverse phenotypic attributes; and that exposure to the environment rapidly and preferentially expands the MR1-5-OP-RU tetramer+TRAV1-2+ population of MR1T cells, which becomes the predominant population of functional MR1T cells early during childhood.
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影响因子：
4
作者：
Gherardin NA;Souter MN;Koay HF;Mangas KM;Seemann T;Stinear TP;Eckle SB;Berzins SP;d'Udekem Y;Konstantinov IE;Fairlie DP;Ritchie DS;Neeson PJ;Pellicci DG;Uldrich AP;McCluskey J;Godfrey DI
通讯作者：
Godfrey DI
影响因子：
9.8
作者：
Martin E;Treiner E;Duban L;Guerri L;Laude H;Toly C;Premel V;Devys A;Moura IC;Tilloy F;Cherif S;Vera G;Latour S;Soudais C;Lantz O
通讯作者：
Lantz O
DOI：
10.1084/jem.20171739
发表时间：
2018-02-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Ben Youssef G;Tourret M;Salou M;Ghazarian L;Houdouin V;Mondot S;Mburu Y;Lambert M;Azarnoush S;Diana JS;Virlouvet AL;Peuchmaur M;Schmitz T;Dalle JH;Lantz O;Biran V;Caillat-Zucman S
通讯作者：
Caillat-Zucman S
影响因子：
5.4
作者：
Arlehamn, Cecilia S. Lindestam;Lewinsohn, David;Lewinsohn, Deborah
通讯作者：
Lewinsohn, Deborah
DOI：
10.1126/science.aax6624
发表时间：
2019-10-25
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Constantinides MG;Link VM;Tamoutounour S;Wong AC;Perez-Chaparro PJ;Han SJ;Chen YE;Li K;Farhat S;Weckel A;Krishnamurthy SR;Vujkovic-Cvijin I;Linehan JL;Bouladoux N;Merrill ED;Roy S;Cua DJ;Adams EJ;Bhandoola A;Scharschmidt TC;Aubé J;Fischbach MA;Belkaid Y
通讯作者：
Belkaid Y