HCV治疗中PD-1/PD-L1信号免疫调控作用的研究概况

An overview of immunoregulatory roles of PD-1/PD-L1 in HCV treatment

丙型肝炎病毒(hepatitis C virus,HCV)感染以其高慢性化、高肝纤维化和高肝细胞癌发生率,已经成为一个全球性的公共卫生问题。本综述拟概述HCV感染和治疗、PD-1(programmed cell death 1 gene,PD-1)高表达与免疫应答在HCV感染中的关联。在抗-HCV治疗中,提高免疫细胞调控能力是决定治疗效果的关键因素之一。慢性HCV感染中,有功能障碍的HCV特异性CD8^+T细胞上PD-1表达水平升高,阻断PD-1/PD-L1(programmed death-ligand 1,PD-L1)信号后,T细胞调控功能部分恢复;PD-1/PD-L1信号的增强,不仅抑制细胞毒性T细胞的功能,还影响CD8^+T细胞的分化。临床上,阻断PD-1/PD-L1信号通路后,抗-HCV免疫应答水平增强。因此,加强对HCV感染诱导PD-1高表达的机制和HCV特异性T细胞功能障碍发生的机制研究,将有助于促进慢性HCV感染的预防性和治疗性疫苗的研发,并最终改善HCV治疗的效果。

As with high incidence of chronicity, hepatic fibrosis and hepatocellular carcinoma （HCC） , hepatitis C virus （HCV） infection has become global problems of public hygiene. How to enhance the immunoregulatory ability of im- munocytes turned out to be one of the key factors influencing the results of anti-HCV therapy. This review will summarize the survey of HCV infection and therapy, the association of PD-I with anti-HCV immune response, and the roles of PD-1/ PD-L1 blocking in anti-HCV. In chronic HCV patients, PD-I level on dysfunctional HCV-specific CD8 ＋ T cells was in- creased, and the virus-induced T cell dysfunction could be partly restored by PD-1/PD-L1 blocking. In HCV infection, the increased PD-1/PD-L1 inhibitory signal participates in the CTLs inhibition and CD8 ＋ T cell differentiation. It＇ s also reported in clinically that anti-HCV immune response could be enhanced by PD-1/PD-L1 blocking. Therefore, it＇ s of great impor- tance to explore the mechanisms of HCV-induced PD-1 increasing and PD-1/PD-LI inhibitory signal induced T cell dysfunc- tion, which will contribute to the prophylactic and therapeutic vaccines for HCV infection, and lastly better HCV therapy.