Africa Health Research Institute and.
School of Laboratory Medicine, Nelson Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
J Clin Invest. 2020 Jan 2;130(1):214-230. doi: 10.1172/JCI130711.
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.
识别分枝杆菌抗原的非常规 T 细胞是作为抗结核分枝杆菌（TB）疫苗靶点的重要候选物。这包括供体非限制 T 细胞（DURTs），如黏膜相关不变 T 细胞（MAITs）、CD1 限制 T 细胞和 γδ T 细胞。我们利用 DURTs 和 γδ T 细胞受体（TCRs）的独特性质，通过全球 TCR 测序来研究这些 T 细胞在人类肺部 TB 中的参与情况。利用手术肺切除术，我们研究了来自 TB 感染个体的肺组织和匹配血液中 TCR 的分布、频率和特征。尽管 MAITs 和某些 CD1 限制 T 细胞从血液中耗竭，但我们发现 DURT 库在肺部得到了很好的保留，无论疾病状态或 HIV 合并感染如何。相比之下，TCRδ 库在肺部呈高度偏倚分布，以 Vδ1 为主导，具有高度局部化的克隆扩增，与非循环肺驻留 γδ T 细胞群体一致。这些数据表明，库测序是跟踪疾病过程中 T 细胞亚群的有力工具。
