Cytomegalovirus (CMV) infection is responsible for significant morbidity and mortality in immunocompromised patients, namely solid organ and hematopoietic cell transplant recipients, and can induce congenital infection in neonates. There is currently an unmet need for new management and treatment strategies. Establishment of an anti‐CMV immune response is critical in order to control CMV infection. The two main human T cells involved in HCMV‐specific response are αβ and non‐Vγ9Vδ2 T cells that belong to γδ T cell compartment. CMV‐induced non‐Vγ9Vδ2 T cells harbor a specific clonal expansion and a phenotypic signature, and display effector functions against CMV. So far, only two main molecular mechanisms underlying CMV sensing have been identified. Non‐Vγ9Vδ2 T cells can be activated either by stress‐induced surface expression of the γδT cell receptor (TCR) ligand annexin A2, or by a multimolecular stress signature composed of the γδTCR ligand endothelial protein C receptor and co‐stimulatory signals such as the ICAM‐1‐LFA‐1 axis. All this basic knowledge can be harnessed to improve the clinical management of CMV infection in at‐risk patients. In particular, non‐Vγ9Vδ2 T cell monitoring could help better stratify the risk of infection and move forward a personalized medicine. Moreover, recent advances in cell therapy protocols open the way for a non‐Vγ9Vδ2 T cell therapy in immunocompromised patients.

中文翻译：

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了解人类 γδ T 细胞生物学以更好地管理巨细胞病毒感染

巨细胞病毒 (CMV) 感染导致免疫功能低下患者（即实体器官和造血细胞移植受者）的显着发病率和死亡率，并可诱发新生儿先天性感染。目前对新的管理和治疗策略的需求未得到满足。建立抗 CMV 免疫反应对于控制 CMV 感染至关重要。参与 HCMV 特异性反应的两种主要人类 T 细胞是属于 γδ T 细胞区室的 αβ 和非 Vγ9Vδ2 T 细胞。CMV 诱导的非 Vγ9Vδ2 T 细胞具有特定的克隆扩增和表型特征，并显示出针对 CMV 的效应子功能。到目前为止，仅发现了 CMV 传感的两种主要分子机制。非 Vγ9Vδ2 T 细胞可以通过应激诱导的 γδT 细胞受体 (TCR) 配体膜联蛋白 A2 的表面表达，或由 γδTCR 配体内皮蛋白 C 受体和共刺激信号（如ICAM-1-LFA-1 轴。所有这些基础知识都可以用来改善高危患者 CMV 感染的临床管理。特别是，非 Vγ9Vδ2 T 细胞监测可以帮助更好地分层感染风险并推进个性化医疗。此外，细胞治疗方案的最新进展为免疫功能低下患者的非 Vγ9Vδ2 T 细胞治疗开辟了道路。所有这些基础知识都可以用来改善高危患者 CMV 感染的临床管理。特别是，非 Vγ9Vδ2 T 细胞监测可以帮助更好地分层感染风险并推进个性化医疗。此外，细胞治疗方案的最新进展为免疫功能低下患者的非 Vγ9Vδ2 T 细胞治疗开辟了道路。所有这些基础知识都可以用来改善高危患者 CMV 感染的临床管理。特别是，非 Vγ9Vδ2 T 细胞监测可以帮助更好地分层感染风险并推进个性化医疗。此外，细胞治疗方案的最新进展为免疫功能低下患者的非 Vγ9Vδ2 T 细胞治疗开辟了道路。