Functional dichotomy of Vδ2 γδ T cells in chronic hepatitis C virus infections: role in cytotoxicity but not for IFN-γ production.
Functional dichotomy of Vδ2 γδ T cells in chronic hepatitis C virus infections: role in cytotoxicity but not for IFN-γ production.
复制标题
慢性丙型肝炎病毒感染中 Vdelta2 gammadelta T 细胞的功能二分法：在细胞毒性中起作用，但在 IFN-gamma 产生中不起作用。
DOI：
10.1038/srep26296
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发表时间：
2016-05-19
影响因子：
4.6
通讯作者：
Zhang D
中科院分区：
文献类型：
--
作者：
Yin W;Tong S;Zhang Q;Shao J;Liu Q;Peng H;Hu H;Peng M;Hu P;Ren H;Tian Z;Zhang D
Vδ2 γδ (Vδ2) T细胞是人类主要的γδ T细胞亚群，具有广泛的抗肿瘤和抗感染活性；然而，它们在慢性丙型肝炎病毒（HCV）感染中的确切作用尚不清楚。在这项研究中，我们分析了43名hcv感染患者的Vδ2 T细胞的表型和功能，并与39名健康对照（hc）进行了比较。hcv感染患者的Vδ2 T细胞被激活并分化为效应细胞。患者的Vδ2 T细胞表达的自然杀伤（NK）细胞标志物CD56和CD16水平明显高于hcc，获得细胞毒性NK样表型。在血清ALT水平升高的hcv感染患者中，Vδ2 T细胞表型与细胞溶解效应分子表达增加相关。令人惊讶的是，患者体内的Vδ2 T细胞产生IFN-γ的能力明显受损。进一步的体外和体内分析表明，在HCV感染期间诱导的干扰素-α导致Vδ2 T细胞功能偏向于细胞毒性。这些结果表明，在慢性HCV感染中，Vδ2 T细胞的功能分为两种：一种是细胞毒性作用，另一种是IFN-γ产生作用，这可能有助于肝脏炎症和HCV的持久性。
Vδ2 γδ (Vδ2) T cells, a major human γδ T cell subset, exhibit broad anti-tumor and anti-infective activity; however, their precise role in chronic hepatitis C virus (HCV) infections remains unclear. In this study, we analyzed the phenotype and function of Vδ2 T cells in 43 HCV-infected patients compared to 39 healthy controls (HCs). Vδ2 T cells from HCV-infected patients were activated and differentiated into effector cells. Vδ2 T cells in patients expressed significantly higher levels of natural killer (NK) cell markers CD56 and CD16 than in HCs, acquiring cytotoxic NK-like phenotype. The Vδ2 T cell phenotype was associated with increased cytolytic effector molecules expression in HCV-infected patients with elevated serum ALT levels. Surprisingly, Vδ2 T cells in patients had a markedly impaired capacity to produce IFN-γ. Further in vitro and in vivo analysis showed that interferon-α, which was induced during HCV infection, caused Vδ2 T cell function bias toward cytotoxicity. These results suggest a functional dichotomy for Vδ2 T cells in chronic HCV infections: a role in cytotoxicity but not for IFN-γ production, which may contribute to both the liver inflammation and HCV persistence.