Université de Bordeaux , Bordeaux , France ; UMR 5164, Centre National de la Recherche Scientifique , Bordeaux , France ; Service de Néphrologie, Transplantation, Dialyse, Centre Hospitalier Universitaire de Bordeaux , Bordeaux , France.
Université de Bordeaux , Bordeaux , France ; UMR 5164, Centre National de la Recherche Scientifique , Bordeaux , France.
Front Immunol. 2015 Jan 21;6:3. doi: 10.3389/fimmu.2015.00003. eCollection 2015.
Despite effective anti-viral therapies, cytomegalovirus (CMV) is still associated with direct (CMV disease) and indirect effects (rejection and poor graft survival) in kidney transplant recipients. Recently, an unconventional T cell population (collectively designated as Vδ2(neg) γδ T cells) has been characterized during the anti-CMV immune response in all solid-organ and bone-marrow transplant recipients, neonates, and healthy people. These CMV-induced Vδ2(neg) γδ T cells undergo a dramatic and stable expansion after CMV infection, in a conventional "adaptive" manner. Similarly, as CMV-specific CD8+ αβ T cells, they exhibit an effector/memory TEMRA phenotype and cytotoxic effector functions. Activation of Vδ2(neg) γδ T cells by CMV-infected cells involves the γδ T cell receptor (TCR) and still ill-defined co-stimulatory molecules such as LFA-1. A multiple of Vδ2(neg) γδ TCR ligands are apparently recognized on CMV-infected cells, the first one identified being the major histocompatibility complex-related molecule endothelial protein C receptor. A singularity of CMV-induced Vδ2(neg) γδ T cells is to acquire CD16 expression and to exert an antibody-dependent cell-mediated inhibition on CMV replication, which is controlled by a specific cytokine microenvironment. Beyond the well-demonstrated direct anti-CMV effect of Vδ2(neg) γδ T cells, unexpected indirect effects of these cells have been also observed in the context of kidney transplantation. CMV-induced Vδ2(neg) γδ T cells have been involved in surveillance of malignancy subsequent to long-term immunosuppression. Moreover, CMV-induced CD16+ γδ T cells are cell effectors of antibody-mediated rejection of kidney transplants, and represent a new physiopathological contribution to the well-known association between CMV infection and poor graft survival. All these basic and clinical studies paved the road to the development of a future γδ T cell-based immunotherapy. In the meantime, γδ T cell monitoring should prove a valuable immunological biomarker in the management of CMV infection.
尽管有有效的抗病毒疗法，巨细胞病毒（CMV）仍然与肾移植受者的直接（CMV 疾病）和间接影响（排斥和移植物存活率降低）有关。最近，在所有实体器官和骨髓移植受者、新生儿和健康人群的抗 CMV 免疫反应中，已经描述了一种非常规 T 细胞群体（统称为 Vδ2(neg)γδ T 细胞）。这些 CMV 诱导的 Vδ2(neg)γδ T 细胞在 CMV 感染后以传统的“适应性”方式经历剧烈和稳定的扩增。同样，与 CMV 特异性 CD8+αβ T 细胞一样，它们表现出效应/记忆 TEMRA 表型和细胞毒性效应功能。CMV 感染细胞激活 Vδ2(neg)γδ T 细胞涉及 γδ T 细胞受体（TCR）和仍然定义不明确的共刺激分子，如 LFA-1。CMV 感染细胞上显然可以识别多种 Vδ2(neg)γδ TCR 配体，第一个被鉴定的是主要组织相容性复合物相关分子内皮蛋白 C 受体。CMV 诱导的 Vδ2(neg)γδ T 细胞的一个独特之处是获得 CD16 表达，并对 CMV 复制发挥抗体依赖性细胞介导的抑制作用，这受特定细胞因子微环境的控制。除了已经证明的 Vδ2(neg)γδ T 细胞对 CMV 的直接抗病毒作用外，在肾移植中还观察到这些细胞的意外间接作用。CMV 诱导的 Vδ2(neg)γδ T 细胞参与长期免疫抑制后恶性肿瘤的监测。此外，CMV 诱导的 CD16+γδ T 细胞是肾移植抗体介导排斥反应的细胞效应物，代表了 CMV 感染与移植物存活率降低之间已知关联的新的病理生理贡献。所有这些基础和临床研究为未来基于 γδ T 细胞的免疫疗法铺平了道路。与此同时，γδ T 细胞监测应该被证明是 CMV 感染管理中的有价值的免疫生物学标志物。
