γδ T cells contribute to host immune defense uniquely; but how they function in different stages (e.g., acute versus chronic) of a specific infection remains unclear. As the role of γδ T cells in early, active Mycobacterium tuberculosis (Mtb) infection is well documented, we focused on elucidating the γδ T cell response in persistent or controlled Mtb infection. Systems analysis of circulating γδ T cells from a South African adolescent cohort identified a distinct population of CD8+ γδ T cells that expanded in this state. These cells had features indicative of persistent antigenic exposure but were robust cytolytic effectors and cytokine/chemokine producers. While these γδ T cells displayed an attenuated response to TCR-mediated stimulation, they expressed Natural Killer (NK) cell receptors and had robust CD16 (FcγRIIIA)-mediated cytotoxic response, suggesting alternative ways for γδ T cells to control this stage of the infection. Despite this NK- like functionality, the CD8+ γδ T cells consisted of highly expanded clones, which utilized TCRs with different Vγ/δ pairs. Theses TCRs could respond to an Mtb-lysate, but not to phosphoantigens, which are components of Mtb-lysate that activate γδ T cells in acute Mtb infection, indicating that the CD8+ γδ T cells were induced in a stage-specific, antigen-driven manner. Indeed, trajectory analysis showed that these γδ T cells arose from naive cells that had traversed distinct differentiation paths in this infection stage. Importantly, increased levels of CD8+ γδ T cells were also found in other chronic inflammatory conditions, including cardiovascular disease and cancer, suggesting that persistent antigenic exposure may lead to similar γδ T cell responses.

中文翻译：

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抗原识别在结核分枝杆菌感染控制阶段γδT细胞反应中的作用

γδ T 细胞独特地有助于宿主免疫防御；但它们如何在特定感染的不同阶段（例如，急性与慢性）发挥作用仍不清楚。由于γδ T 细胞在早期活动性结核分枝杆菌(Mtb) 感染中的作用有据可查，我们专注于阐明持续或受控 Mtb 感染中的γδ T 细胞反应。对来自南非青少年队列的循环γδ T 细胞的系统分析确定了在这种状态下扩增的独特 CD8+ γδ T 细胞群。这些细胞具有表明持续抗原暴露的特征，但它们是强大的细胞溶解效应物和细胞因子/趋化因子生产者。而这些γδT 细胞对 TCR 介导的刺激表现出减弱的反应，它们表达自然杀伤 (NK) 细胞受体，并具有强大的 CD16 (Fc γ RIIIA) 介导的细胞毒性反应，这表明γδ T 细胞控制这一感染阶段的替代方法。尽管具有类似 NK 的功能，但 CD8+ γδ T 细胞由高度扩增的克隆组成，它们利用具有不同 V γ / δ对的TCR 。这些 TCR 可以对 Mtb 裂解物作出反应，但对磷酸抗原没有反应，磷酸抗原是 Mtb 裂解物中在急性 Mtb 感染中激活γδ T 细胞的组分，表明 CD8+ γδT 细胞以阶段特异性、抗原驱动的方式被诱导。事实上，轨迹分析表明，这些γδ T 细胞来自在这个感染阶段穿过不同分化路径的幼稚细胞。重要的是，在其他慢性炎症性疾病（包括心血管疾病和癌症）中也发现了 CD8+ γδ T 细胞水平升高，这表明持续的抗原暴露可能导致类似的γδ T 细胞反应。