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结核患者与健康结核分枝杆菌暴露对照者外周血黏膜相关不变 T 细胞。

Peripheral Blood Mucosal-Associated Invariant T Cells in Tuberculosis Patients and Healthy Mycobacterium tuberculosis-Exposed Controls.

机构信息

Division of Rheumatology, Immunity and Inflammation, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.

South African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.

出版信息

J Infect Dis. 2020 Aug 17;222(6):995-1007. doi: 10.1093/infdis/jiaa173.

Abstract

BACKGROUND

In human blood, mucosal-associated invariant T (MAIT) cells are abundant T cells that recognize antigens presented on non-polymorphic major histocompatibility complex-related 1 (MR1) molecules. The MAIT cells are activated by mycobacteria, and prior human studies indicate that blood frequencies of MAIT cells, defined by cell surface markers, decline during tuberculosis (TB) disease, consistent with redistribution to the lungs.

METHODS

We tested whether frequencies of blood MAIT cells were altered in patients with TB disease relative to healthy Mycobacterium tuberculosis-exposed controls from Peru and South Africa. We quantified their frequencies using MR1 tetramers loaded with 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil.

RESULTS

Unlike findings from prior studies, frequencies of blood MAIT cells were similar among patients with TB disease and latent and uninfected controls. In both cohorts, frequencies of MAIT cells defined by MR1-tetramer staining and coexpression of CD161 and the T-cell receptor alpha variable gene TRAV1-2 were strongly correlated. Disease severity captured by body mass index or TB disease transcriptional signatures did not correlate with MAIT cell frequencies in patients with TB.

CONCLUSIONS

Major histocompatibility complex (MHC)-related 1-restrictied MAIT cells are detected at similar levels with tetramers or surface markers. Unlike MHC-restricted T cells, blood frequencies of MAIT cells are poor correlates of TB disease but may play a role in pathophysiology.

摘要

背景

在人类血液中,黏膜相关不变 T(MAIT)细胞是大量识别非多态性主要组织相容性复合体相关 1(MR1)分子上呈递抗原的 T 细胞。MAIT 细胞被分枝杆菌激活,先前的人体研究表明,通过细胞表面标志物定义的 MAIT 细胞在结核病(TB)疾病期间血液中的频率下降,与向肺部重新分布一致。

方法

我们检测了秘鲁和南非的 TB 病患者与潜伏和未感染对照者之间,血液 MAIT 细胞的频率是否发生改变。我们使用负载 5-(2-氧代丙基二亚氨基)-6-D-核糖基氨基尿嘧啶的 MR1 四聚体来量化它们的频率。

结果

与先前的研究结果不同,TB 病患者与潜伏和未感染对照者的血液 MAIT 细胞频率相似。在两个队列中,通过 MR1-四聚体染色和 CD161 共表达以及 T 细胞受体α可变基因 TRAV1-2 定义的 MAIT 细胞频率具有很强的相关性。TB 病转录特征或身体质量指数(BMI)所捕捉的疾病严重程度与 TB 病患者的 MAIT 细胞频率无关。

结论

MAIT 细胞与四聚体或表面标志物一样以相似的水平被 MHC 相关 1 限制。与 MHC 限制的 T 细胞不同,MAIT 细胞的血液频率与 TB 病相关性差,但可能在发病机制中发挥作用。

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