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High expression of CD26 accurately identifies human bacteria-reactive MR1-restricted MAIT cells

机译:CD26的高表达可准确识别人类细菌反应性MR1限制的MAIT细胞

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Mucosa-associated invariant T (MAIT) cells express the semi-invariant T-cell receptor TRAV1-2 and detect a range of bacteria and fungi through the MHC-like molecule MR1. However, knowledge of the function and phenotype of bacteria-reactive MR1-restricted TRAV1-2(+) MAIT cells from human blood is limited. We broadly characterized the function of MR1-restricted MAIT cells in response to bacteria-infected targets and defined a phenotypic panel to identify these cells in the circulation. We demonstrated that bacteria-reactive MR1-restricted T cells shared effector functions of cytolytic effector CD8(+) T cells. By analysing an extensive panel of phenotypic markers, we determined that CD26 and CD161 were most strongly associated with these T cells. Using FACS to sort phenotypically defined CD8(+) subsets we demonstrated that high expression of CD26 on CD8(+)TRAV1-2(+) cells identified with high specificity and sensitivity, bacteria-reactive MR1-restricted T cells from human blood. CD161(hi) was also specific for but lacked sensitivity in identifying all bacteria-reactive MR1-restricted T cells, some of which were CD161(dim). Using cell surface expression of CD8, TRAV1-2, and CD26(hi) in the absence of stimulation we confirm that bacteria-reactive T cells are lacking in the blood of individuals with active tuberculosis and are restored in the blood of individuals undergoing treatment for tuberculosis.
机译:粘膜相关不变T(MAIT)细胞表达半不变T细胞受体TRAV1-2,并通过类MHC分子MR1检测一系列细菌和真菌。但是,从人类血液中细菌反应性的MR1限制性TRAV1-2(+)MAIT细胞的功能和表型的知识是有限的。我们广泛表征了MR1限制的MAIT细胞对细菌感染的靶标的反应功能,并定义了一个表型面板来识别循环中的这些细胞。我们证明,细菌反应性的MR1限制T细胞共享细胞溶解效应CD8(+)T细胞的效应功能。通过分析广泛的表型标记,我们确定CD26和CD161与这些T细胞最密切相关。使用流式细胞仪对表型定义的CD8(+)子集进行排序,我们证明了CD26在CD8(+)TRAV1-2(+)细胞上的高表达具有很高的特异性和敏感性,是人类血液中细菌反应性的MR1限制性T细胞。 CD161(hi)对鉴定所有细菌反应性的MR1限制性T细胞(其中一些是CD161(dim))也具有特异性,但缺乏敏感性。使用CD8,TRAV1-2和CD26(hi)在无刺激的情况下的细胞表面表达,我们证实细菌感染性T细胞在活动性结核病患者的血液中缺乏,并且在接受治疗的个体的血液中得以恢复结核。

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