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作 者:肖雯[1] 裴家平 季晓伟[2] 石丽萍[2] 邓小昭[1,3] 蒋龙凤[4] 张锦海[3] 王长军[3]
机构地区:[1]中国药科大学生命科学与技术学院微生物与生化药学系,江苏南京210009 [2]南京医科大学基础医学院生物化学与分子生物学系,江苏南京210029 [3]南京军区疾病预防控制中心疾病预防控制所,江苏南京210002 [4]南京医科大学第一附属医院感染病科,江苏南京210029
出 处:《中华疾病控制杂志》2017年第2期200-205,共6页Chinese Journal of Disease Control & Prevention
基 金:国家自然科学基金项目(81573213;81172724);江苏省自然科学基金项目(BK20151089)
摘 要: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.
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