Peng P, Ji Y Q, Zhao N H, Liu T, Wang H, Yao J
Department of Gastroenterology, Shanxi Provincial People's Hospital, Taiyuan 030031, China.
Department of Biochemistry and Molecular Biology, Basic Medical College, Shanxi Medical University, Taiyuan 030000, China.
Zhonghua Gan Zang Bing Za Zhi. 2023 Apr 20;31(4):422-427. doi: 10.3760/cma.j.cn501113-20220205-00056.
T lymphocyte exhaustion is an important component of immune dysfunction. Therefore, exploring peripheral blood-exhausted T lymphocyte features in patients with hepatitis B virus-related acute-on-chronic liver failure may provide potential therapeutic target molecules for ACLF immune dysfunction. Six cases with HBV-ACLF and three healthy controls were selected for T-cell heterogeneity detection using the single-cell RNA sequencing method. In addition, exhausted T lymphocyte subpopulations were screened to analyze their gene expression features, and their developmental trajectories quasi-timing. An independent sample t-test was used to compare the samples between the two groups. Peripheral blood T lymphocytes in HBV-ACLF patients had different differentiation trajectories with different features distinct into eight subpopulations. Among them, the CD4(+)TIGIT(+) subsets ( = 0.007) and CD8(+)LAG3(+) ( = 0.010) subsets with highly exhausted genes were significantly higher than those in healthy controls. Quasi-time analysis showed that CD4(+)TIGIT(+) and CD8(+)LAG3(+) subsets appeared in the late stage of T lymphocyte differentiation, suggesting the transition of T lymphocyte from naïve-effector-exhausted during ACLF pathogenesis. There is heterogeneity in peripheral blood T lymphocyte differentiation in patients with HBV-ACLF, and the number of exhausted T cells featured by CD4(+)TIGIT(+)T cell and CD8(+)LAG3(+) T cell subsets increases significantly, suggesting that T lymphocyte immune exhaustion is involved in the immune dysfunction of HBV-ACLF, thereby identifying potential effective target molecules for improving ACLF patients' immune function.
T淋巴细胞耗竭是免疫功能障碍的重要组成部分。因此，探索乙型肝炎病毒相关慢加急性肝衰竭患者外周血中耗竭T淋巴细胞的特征，可能为慢加急性肝衰竭免疫功能障碍提供潜在的治疗靶点分子。选取6例乙型肝炎病毒相关慢加急性肝衰竭患者和3例健康对照，采用单细胞RNA测序方法进行T细胞异质性检测。此外，筛选耗竭T淋巴细胞亚群，分析其基因表达特征及其发育轨迹的准时序。采用独立样本t检验比较两组样本。乙型肝炎病毒相关慢加急性肝衰竭患者外周血T淋巴细胞具有不同的分化轨迹，可分为8个具有不同特征的亚群。其中，基因高度耗竭的CD4(+)TIGIT(+)亚群（P = 0.007）和CD8(+)LAG3(+)亚群（P = 0.010）显著高于健康对照。准时序分析显示，CD4(+)TIGIT(+)和CD8(+)LAG3(+)亚群出现在T淋巴细胞分化后期，提示在慢加急性肝衰竭发病过程中T淋巴细胞从幼稚-效应-耗竭的转变。乙型肝炎病毒相关慢加急性肝衰竭患者外周血T淋巴细胞分化存在异质性，以CD4(+)TIGIT(+)T细胞和CD8(+)LAG3(+)T细胞亚群为特征的耗竭T细胞数量显著增加，提示T淋巴细胞免疫耗竭参与乙型肝炎病毒相关慢加急性肝衰竭的免疫功能障碍，从而为改善慢加急性肝衰竭患者免疫功能确定潜在有效的靶点分子。
