Li Jing, Cheng Lisha, Jia Haoyu, Liu Chun, Wang Siqi, Liu Yun, Shen Yue, Wu Shengdi, Meng Fanli, Zheng Beishi, Yang Changqing, Jiang Wei
Department of Gastroenterology and Hepatology Tongji Hospital School of Medicine Tongji University Shanghai China.
Department of Gastroenterology and Hepatology Zhongshan Hospital Fudan University Shanghai China.
Clin Transl Immunology. 2021 Nov 2;10(11):e1353. doi: 10.1002/cti2.1353. eCollection 2021.
This study aimed to determine the role of CD161CD4 T cells in chronic hepatitis B virus (HBV) infection.
A total of 94 patients with chronic hepatitis B (CHB), 73 with liver cirrhosis (LC) and 28 healthy controls were enrolled to determine frequency, cytokine production and chemokine receptor expression of circulating CD161CD4 T cells. Among these, 50 CHB and 34 LC patients were followed up for a period of 52-week entecavir monotherapy to assess the association of CD161CD4 T cells with seroconversion of HBV e antigen (HBeAg). In addition, 15 patients with hepatocellular carcinoma (HCC) and 15 with hepatic haemangioma (HHA) were enrolled to compare the paired circulating and intrahepatic CD161CD4 T cells.
CD161CD4 T cells were found to accumulate in the circulation of HBV cohorts, which showed a significant correlation with the clinical parameters of disease progression. In addition, higher numbers of circulating CD161CD4 T cells were associated with an improved serological response of HBeAg to antiviral treatment. Moreover, CD161CD4 T cells as compared to homologous CD161CD4 T cells produced more pro-inflammatory cytokines including interleukin (IL)-17 and interferon (IFN)-γ and expressed higher levels of liver-homing chemokine receptors including CCR6, CXCR6 and CX3CR1. Notably, a significant enrichment of CD161CD4 T cell subsets co-expressing IFN-γ and IL-17 was observed in HBV-associated cirrhotic livers. During co-cultures, circulating CD161CD4 T cells in the chronic HBV setting exhibited prominent pro-fibrogenic effects by regulating primary hepatic stellate cells through a regenerative IFN-γ/IL-23/IL-17 axis.
In chronic HBV infection, CD161CD4 T cells play antiviral, pro-inflammatory and pro-fibrogenic roles.
本研究旨在确定CD161⁺CD4⁺ T细胞在慢性乙型肝炎病毒（HBV）感染中的作用。
共纳入94例慢性乙型肝炎（CHB）患者、73例肝硬化（LC）患者和28例健康对照者，以确定循环CD161⁺CD4⁺ T细胞的频率、细胞因子产生和趋化因子受体表达。其中，50例CHB患者和34例LC患者接受了为期52周的恩替卡韦单药治疗，以评估CD161⁺CD4⁺ T细胞与HBV e抗原（HBeAg）血清学转换的相关性。此外，纳入15例肝细胞癌（HCC）患者和15例肝血管瘤（HHA）患者，比较配对的循环和肝内CD161⁺CD4⁺ T细胞。
发现CD161⁺CD4⁺ T细胞在HBV感染者的循环中积聚，这与疾病进展的临床参数显著相关。此外，循环CD161⁺CD4⁺ T细胞数量增加与HBeAg对抗病毒治疗的血清学反应改善相关。此外，与同源CD161⁺CD4⁺ T细胞相比，CD161⁺CD4⁺ T细胞产生更多促炎细胞因子，包括白细胞介素（IL）-17和干扰素（IFN）-γ，并表达更高水平的肝脏归巢趋化因子受体，包括CCR6、CXCR6和CX3CR1。值得注意的是，在HBV相关肝硬化肝脏中观察到共表达IFN-γ和IL-17的CD161⁺CD4⁺ T细胞亚群显著富集。在共培养过程中，慢性HBV环境中的循环CD161⁺CD4⁺ T细胞通过再生IFN-γ/IL-23/IL-17轴调节原代肝星状细胞，表现出显著的促纤维化作用。
在慢性HBV感染中，CD161⁺CD4⁺ T细胞发挥抗病毒、促炎和促纤维化作用。
