The response of gamma delta (γδ) T cells in the acute versus chronic phases of the same infection is unclear. How γδ T cells function in acute Mycobacterium tuberculosis (Mtb) infection is well characterized, but their response during persistent Mtb infection is not well understood, even though most infections with Mtb manifest as a chronic, clinically asymptomatic state. Here, we analyze peripheral blood γδ T cells from a South African adolescent cohort and show that a unique CD8 + γδ T cell subset with features of “memory inflation” expands in chronic Mtb infection. These cells are hyporesponsive to T cell receptor (TCR)–mediated signaling but, like NK cells, can mount robust CD16-mediated cytotoxic responses. These CD8 + γδ T cells comprise a highly focused TCR repertoire, with clonotypes that are Mycobacterium specific but not phosphoantigen reactive. Using multiparametric single-cell pseudo-time trajectory analysis, we identified the differentiation paths that these CD8 + γδ T cells follow to develop into effectors in this infection state. Last, we found that circulating CD8 + γδ T cells also expand in other chronic inflammatory conditions, including cardiovascular disease and cancer, suggesting that persistent antigenic exposure may drive similar γδ T cell effector programs and differentiation fates.

中文翻译：

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NK 样 CD8 + γδ T 细胞在持续结核分枝杆菌感染中扩增


γδ (γδ) T 细胞在同一感染的急性期和慢性期的反应尚不清楚。 γδ T 细胞如何在急性期发挥作用结核分枝杆菌结核分枝杆菌（Mtb）感染的特征已得到很好的表征，但尽管大多数结核分枝杆菌感染表现为慢性、临床无症状状态，但其在持续性结核分枝杆菌感染期间的反应尚不清楚。在这里，我们分析了来自南非青少年队列的外周血 γδ T 细胞，并表明独特的 CD8 +具有“记忆膨胀”特征的γδT细胞亚群在慢性结核菌感染中扩增。这些细胞对 T 细胞受体 (TCR) 介导的信号传导反应低下，但与 NK 细胞一样，可以产生强大的 CD16 介导的细胞毒性反应。这些CD8 + γδ T 细胞包含高度集中的 TCR 库，其克隆型为分枝杆菌具有特异性但不具有磷酸抗原反应性。使用多参数单细胞伪时间轨迹分析，我们确定了这些 CD8 的分化路径+在这种感染状态下，γδ T 细胞随后发育成效应细胞。最后，我们发现流通的CD8 + γδ T 细胞也在其他慢性炎症条件下扩增，包括心血管疾病和癌症，这表明持续的抗原暴露可能驱动类似的 γδ T 细胞效应程序和分化命运。