Cytomegalovirus is a major infectious cause of mortality and morbidity following transplantation. We have previously demonstrated that the tissue-associated adaptive Vδ2^neg γδ T-cells are key effectors responding to CMV and associated to recovery, contrasting with their innate-like circulating counterparts, the Vγ9^posVδ2^pos T-cells that respond to phosphoantigens but not to CMV. A third additional Vγ9^negVδ2^pos subgroup with adaptive functions has been recently described in adults. Here, we demonstrate that these Vγ9^negVδ2^pos T-cells are also components of the CMV immune response while presenting with distinct characteristics from Vδ2^neg γδT-cells. In a cohort of kidney transplant recipients, CMV seropositivity was the unique clinical parameter associated with Vγ9^negVδ2^posT-cell expansion and differentiation. Extensive phenotyping demonstrated their substantial cytotoxic potential and activation during acute CMV primary infection or reinfection. In vitro, Vγ9^negVδ2^pos T-cells responded specifically to CMV-infected cells in a T-Cell Receptor-dependent manner and through strong IFNγ production. Finally, Vγ9^negVδ2^pos T-cells were the only γδT-cell subset which expansion tightly correlated with the severity of CMV disease. To conclude, our results identify a new player in the immune response against CMV and open interesting clinical perspectives for using Vγ9^negVδ2^pos T-cells as an immune marker for CMV disease severity in immunocompromised patients.

中文翻译：

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将独特的 γδ T 细胞亚群表征为 CMV 感染严重程度的特定标志物。

巨细胞病毒是导致移植后死亡和发病的主要传染性原因。我们之前已经证明，组织相关的适应性 Vδ2 ^neg γδ T 细胞是响应 CMV 并与恢复相关的关键效应物，与它们的先天样循环对应物形成对比，Vγ9 ^pos Vδ2 ^pos T 细胞对磷酸抗原有反应但不到 CMV。最近在成人中描述了具有适应性功能的第三个额外的 Vγ9 ^neg Vδ2 ^pos亚组。在这里，我们证明这些 Vγ9 ^neg Vδ2 ^pos T 细胞也是 CMV 免疫反应的组成部分，同时呈现出与 Vδ2 ^neg不同的特征γδT 细胞。在一组肾移植受者中，CMV 血清阳性是与 Vγ9 ^neg Vδ2 ^pos T 细胞扩增和分化相关的独特临床参数。广泛的表型分析表明它们在急性 CMV 原发感染或再感染期间具有显着的细胞毒性潜力和活化作用。在体外， Vγ9 ^neg Vδ2 ^pos T 细胞以 T 细胞受体依赖性方式并通过强大的 IFNγ 产生对 CMV 感染的细胞产生特异性反应。最后，Vγ9^负Vδ2 ^posT 细胞是唯一的 γδT 细胞亚群，其扩增与 CMV 疾病的严重程度密切相关。总之，我们的结果确定了针对 CMV 的免疫反应的新参与者，并为使用 Vγ9 ^neg Vδ2 ^pos T 细胞作为免疫功能低下患者 CMV 疾病严重程度的免疫标志物开辟了有趣的临床前景。