Evaluation of peripheral blood T-lymphocyte subpopulations features in patients with hepatitis B virus-related acute-on-chronic liver failure based on single-cell sequencing technology.
10.3760/cma.j.cn501113-20220205-00056
- Author:
Peng PENG
1
;
Ya Qiu JI
2
;
Ning Hui ZHAO
3
;
Tian LIU
3
;
Han WANG
3
;
Jia YAO
3
Author Information
1. Department of Gastroenterology, Shanxi Provincial People's Hospital, Taiyuan 030031, China.
2. Department of Biochemistry and Molecular Biology, Basic Medical College, Shanxi Medical University, Taiyuan 030000, China.
3. Department of Gastroenterology, Shanxi Bethune Hospital, Taiyuan 030032, China.
- Publication Type:Journal Article
- Keywords:
Acute-on-chronic liver failure;
Single-cell RNA sequencing;
T cell exhaustion;
T lymphocyte
- MeSH:
Humans;
Hepatitis B virus;
Acute-On-Chronic Liver Failure/pathology*;
Hepatitis B, Chronic;
T-Lymphocyte Subsets/pathology*;
Receptors, Immunologic
- From:
Chinese Journal of Hepatology
2023;31(4):422-427
- CountryChina
- Language:Chinese
-
Abstract:
Objective: 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. Methods: 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. Results: 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 (P = 0.007) and CD8(+)LAG3(+) (P = 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. Conclusion: 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.