γδ T细胞在同一感染的急性和慢性阶段的反应尚不清楚。γδ T细胞在急性结核分枝杆菌（Mtb）感染中的功能已经得到了很好的表征，但在持续性Mtb感染期间它们的反应尚不明确，即使大多数Mtb感染表现为慢性且临床无症状状态。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，并展示了一种具有“记忆充气”特征的独特CD8+γδ T细胞亚群在慢性Mtb感染中扩张。这些细胞对T细胞受体（TCR）介导的信号反应较低，但像NK细胞一样，能够产生强大的CD16介导的细胞毒性反应。这些CD8+γδ T细胞包括一个高度专注的TCR亚型，其克隆型是Mycobacterium特异性但不是磷酸抗原反应性的。使用多参数单细胞伪时间轨迹分析，我们确定了这些CD8+γδ T细胞在这种感染状态下发展成为效应者的分化路径。 最后，我们发现循环CD8+γδ T细胞也在其他慢性炎症情况中扩张，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。

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.