Gu Qi, Yin Shengxia, Tong Xin, Rui Fajuan, Zhu Yixuan, Ma Xiaoyan, Huang Rui, Wu Chao, Li Jie
Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China.
J Viral Hepat. 2024 Sep;31(9):557-564. doi: 10.1111/jvh.13958. Epub 2024 May 21.
Chronic hepatitis B virus (HBV) infection is a significant global public health concern, and the clearance of HBV is closely linked to the activity of HBV-specific T cells, which is regulated by various co-suppressor molecules. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) is among these co-suppressor molecules which induces T cell exhaustion by competitively inhibiting CD28 and dampening the function of HBV-specific T cells. CTLA-4 also plays a role in the regulation of T helper (Th) cell differentiation and influences cytokine release. In addition, CTLA-4 can impact glucose metabolism in hepatocellular carcinoma through its interaction with T regulatory (Treg) cells. This review aims to provide a comprehensive overview of the existing literature related to the role of CTLA-4 in HBV patients across different subsets of T cells. Additionally, we propose a discussion on the possible mechanisms through which CTLA-4 may contribute to HBV infection, as well as the development of HBV-induced cirrhosis and hepatocellular carcinoma.
慢性乙型肝炎病毒(HBV)感染是一个重大的全球公共卫生问题,HBV的清除与HBV特异性T细胞的活性密切相关,而HBV特异性T细胞的活性受多种共抑制分子调节。细胞毒性T淋巴细胞相关抗原4(CTLA-4)是这些共抑制分子之一,它通过竞争性抑制CD28并抑制HBV特异性T细胞的功能来诱导T细胞耗竭。CTLA-4在调节辅助性T(Th)细胞分化中也发挥作用,并影响细胞因子的释放。此外,CTLA-4可通过与调节性T(Treg)细胞相互作用影响肝细胞癌中的葡萄糖代谢。本综述旨在全面概述现有文献中CTLA-4在不同T细胞亚群的HBV患者中的作用。此外,我们还对CTLA-4可能导致HBV感染以及HBV诱导的肝硬化和肝细胞癌发生发展的潜在机制进行讨论。