Unconventional T cells that recognize mycobacterial antigens are of great interest as potential vaccine targets against tuberculosis (TB). This includes donor-unrestricted T cells (DURTs), such as mucosa-associated invariant T cells (MAITs), CD1-restricted T cells, and γδ T cells. We exploited the distinctive nature of DURTs and γδ T cell receptors (TCRs) to investigate the involvement of these T cells during TB in the human lung by global TCR sequencing. Making use of surgical lung resections, we investigated the distribution, frequency, and characteristics of TCRs in lung tissue and matched blood from individuals infected with TB. Despite depletion of MAITs and certain CD1-restricted T cells from the blood, we found that the DURT repertoire was well preserved in the lungs, irrespective of disease status or HIV coinfection. The TCRδ repertoire, in contrast, was highly skewed in the lungs, where it was dominated by Vδ1 and distinguished by highly localized clonal expansions, consistent with the nonrecirculating lung-resident γδ T cell population. These data show that repertoire sequencing is a powerful tool for tracking T cell subsets during disease.

中文翻译：

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结核病感染的人肺中供体无限制和γδT细胞库的差异偏斜

识别分枝杆菌抗原的非常规T细胞作为潜在的针对结核病（TB）的疫苗靶标引起了人们的极大兴趣。这包括供体不受限制的T细胞（DURT），例如与粘膜相关的恒定T细胞（MAIT），受CD1限制的T细胞和γδT细胞。我们利用DURT和γδT细胞受体（TCR）的独特性质，通过全局TCR测序研究了这些T细胞在人肺结核中的参与情况。利用外科手术肺切除术，我们研究了肺组织中TCRs的分布，频率和特征，以及来自结核感染者的匹配血液。尽管血液中的MAIT和某些CD1限制性T细胞耗竭，但我们发现DURT血库在肺中保存良好，与疾病状况或HIV合并感染无关。TCRδ曲目，相反，它在肺中高度偏斜，在肺中以Vδ1为主，并以高度局限的克隆性扩张区分开，与非循环性肺驻留γδT细胞群体一致。这些数据表明，曲目库测序是跟踪疾病期间T细胞亚群的强大工具。