Single-Cell RNA Sequencing Shows T-Cell Exhaustion Landscape in the Peripheral Blood of Patients with Hepatitis B Virus-Associated Acute-on-Chronic Liver Failure
- Author:
Jia YAO
1
;
Yaqiu JI
;
Tian LIU
;
Jinjia BAI
;
Han WANG
;
Ruoyu YAO
;
Juan WANG
;
Xiaoshuang ZHOU
Author Information
- Publication Type:Original Article
- From:Gut and Liver 2024;18(3):520-530
- CountryRepublic of Korea
- Language:EN
-
Abstract:
Background/Aims:The occurrence and development of hepatitis B virus-associated acute-onchronic liver failure (HBV-ACLF) is closely related to the immune pathway. We explored the heterogeneity of peripheral blood T cell subsets and the characteristics of exhausted T lymphocytes, in an attempt to identify potential therapeutic target molecules for immune dysfunction in ACLF patients.
Methods:A total of 83,577 T cells from HBV-ACLF patients and healthy controls were screened for heterogeneity by single-cell RNA sequencing. In addition, exhausted T-lymphocyte subsets were screened to analyze their gene expression profiles, and their developmental trajectories were investigated. Subsequently, the expression of exhausted T cells and their capacity in secreting cytokines (interleukin 2, interferon γ, and tumor necrosis factor α) were validated by flow cytometry.
Results:A total of eight stable clusters were identified, among which CD4 + TIGIT + subset and CD8 + LAG-3 + subset, with high expression of exhaust genes, were significantly higher in the HBV-ACLF patients than in normal controls. As shown by pseudotime analysis, T cells experienced a transition from naïve T cells to effector T cells and then exhausted T cells. Flow cytometry confirmed that the CD4 + TIGIT + subset and CD8 + LAG-3 + subset in the peripheral blood of the ACLF patients were significantly higher than those in the healthy controls. Moreover, in vitro cultured CD8 + LAG-3 + T cells were significantly fewer capable of secreting cytokines than CD8 + LAG-3- subset.
Conclusions:Peripheral blood T cells are heterogeneous in HBV-ACLF. The exhausted T cells markedly increase during the pathogenesis of ACLF, suggesting that T-cell exhaustion is involved in the immune dysfunction of HBV-ACLF patients.
