结核性胸膜炎粘膜相关不变性T细胞的研究

Jiangping Li, Changyou Wu
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摘要

mucal - associated Invariant T (MAIT)细胞是一种普遍而独特的先天T细胞群,表达一种进化上保守的不变T细胞受体TCRVα7.2,在粘膜组织部位高频存在,具有对微生物感染的内在反应能力。然而,MAIT细胞在结核分枝杆菌感染部位的局部免疫反应尚不清楚。我们将来自TB (n = 57)的PFMCs与来自TB (n = 57)和HD (n = 50)的PBMCs进行了比较,并表征了这些t细胞的表型和功能。我们的直接离体分析表明,pfmc中MAIT细胞的频率远高于TBP患者的pbmc (P<0.001),但低于HD患者的pbmc (P<0.01)。这些浸润的MAIT细胞表达高水平的组织趋化因子受体(CXCR3hiCXCR4hiCXCR6hiCCR6hiCXCR5hiCCR5hi),并表现出效应记忆表型(CD45RO+CCR7-CD62L-),这表明这些细胞优先积聚到感染的肺病变中。此外,pfmc中的大多数MAIT细胞表达CD69,这是组织驻留记忆T细胞的标记物,这表明这些T细胞特化成独特的组织驻留亚群,从而增强了宿主的区域免疫。此外,来自pfmc的MAIT细胞产生IFN-γ和TNF-α,并表现出细胞毒活性分子CD107a/b,表明多功能M.tb反应性MAIT细胞在局部病变中对M.tb感染起重要作用。本研究表明,mtb反应性MAIT细胞在局部感染部位对mtb的免疫应答中发挥了独特的先天功能。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mucosal-Associated Invariant T Cells in Tuberculosis Pleurisy
Mucosal-Associated Invariant T (MAIT) cells, which is a prevalent and unique innate T-cell population that expresses an evolutionarily conserved invariant T cell receptor TCRVα7.2, are present at high frequencies at mucosal tissue sites and have an intrinsic capacity to respond to microbial infections. However, the local immune responses of MAIT cells at the site of M.tb infection is unclear. We compared the PFMCs from TB (n = 57) with the PBMCs from TB (n = 57) and HD (n = 50), and characterized those T-cell phenotypes and functions. Our direct ex vivo analysis demonstrated that the frequencies of MAIT cells in PFMCs were much higher than those in PBMCs from TBP patients (P<0.001), however, lower than those in PBMCs from HD (P<0.01). Those infiltrating MAIT cells expressed high levels of tissue-tropism chemokine receptors (CXCR3hiCXCR4hiCXCR6hiCCR6hiCXCR5hiCCR5hi) and displayed an effector memory phenotype (CD45RO+CCR7-CD62L-), which indicated preferential accumulating these cells into infected lung lesions. Further, the majority of MAIT cells in PFMCs expressed CD69, a marker for tissue resident memory T cells, which suggested that specialization of these T cells into unique tissue-resident subsets given the host enhanced regional immunity. In addition, MAIT cells from PFMCs produced IFN-γ and TNF-α, and exhibited cytotoxic activity molecules CD107a/b, suggesting that poly functional M.tb-reactive MAIT cells played an significant role against M.tb infection in the local lesions. This study addressed that the M.tb-reactive MAIT cells exerted unique innate functions in immune responses to M.tb at local infection sites.
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