Wei Yan-Yan, Fan Jing, Shan Meng-Xuan, Yin Dan-Dan, Wang Li-Li, Ye Wei, Zhao Wei
Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University Hefei 230022, Anhui, China.
Department of Clinical Research Center, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine Nanjing 210003, Jiangsu, China.
Am J Transl Res. 2022 Feb 15;14(2):942-954. eCollection 2022.
Chronic HBV infection is a serious worldwide health problem that mainly causes liver cirrhosis and hepatocellular carcinoma (HCC). Few studies have explored how T cell exhaustion helps HBV avoid immune system attack and how to reverse that exhaustion. Recently, T cell immunoglobulin and immune receptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) have been identified as coinhibitory receptors, similar to PD-1. This study explores the expression of TIGIT and the T cell function changes in patients with chronic HBV infection.
In this study, we found that the expression of TIGIT on T cells increased significantly in patients with chronic HBV infection. High expression of TIGIT on T cells is associated with functional exhaustion. Importantly, this study demonstrates that blocking TIGIT can reverse T cell exhaustion and restore function in patients with chronic HBV infection.
HBV induces T cell exhaustion by up-regulating the expression of TIGIT. Blocking the TIGIT/PVR signaling pathway can reverse T cell exhaustion, so this discovery provides an immunotherapy target to battle chronic HBV infection.
慢性乙型肝炎病毒（HBV）感染是一个严重的全球性健康问题，主要导致肝硬化和肝细胞癌（HCC）。很少有研究探讨T细胞耗竭如何帮助HBV逃避免疫系统攻击以及如何逆转这种耗竭。最近，T细胞免疫球蛋白和基于免疫受体酪氨酸的抑制基序（ITIM）结构域（TIGIT）已被鉴定为共抑制受体，类似于程序性死亡受体1（PD-1）。本研究探讨慢性HBV感染患者中TIGIT的表达及T细胞功能变化。
在本研究中，我们发现慢性HBV感染患者T细胞上TIGIT的表达显著增加。T细胞上TIGIT的高表达与功能耗竭相关。重要的是，本研究表明阻断TIGIT可逆转慢性HBV感染患者的T细胞耗竭并恢复其功能。
HBV通过上调TIGIT的表达诱导T细胞耗竭。阻断TIGIT/脊髓灰质炎病毒受体（PVR）信号通路可逆转T细胞耗竭，因此这一发现为对抗慢性HBV感染提供了一个免疫治疗靶点。
