Immune Checkpoints Determine the NK/NKT and T Cell Immunity in Chronic Hepatitis B

Chronic hepatitis B virus (CHB) infection poses a serious health threat with high morbidity and mortality, influenced significantly by both innate and adaptive immune responses. The work of innate and adaptive immune systems determines the development and prognosis of CHB. Immune checkpoints (ICs) play a crucial role in regulating the immune response by providing inhibitory or stimulatory signals when interacting with their ligands. However, the precise mechanism by which ICs affect the outcome of CHB patients remains unclear. In this study, we analysed clinical and immune data from 334 CHB patients, along with 17 healthy controls (HC). Using flow cytometry, we assessed immune cell profiles and examined the expression patterns of ICs on innate immune cells (NK/NKT) and adaptive immune cells (T cells) across different stages of CHB. Our analysis revealed distinct immune profiles and differential ICs expression among patients at various disease stages. Moreover, ICs levels were associated with immune cell functions, including cytotoxicity and antiviral cytokines production. We also found that NK and NKT cells may influence T cell function via their ICs expression. Overall, this study provides a comprehensive view of innate and adaptive immunity along with ICs variations in CHB patients, offering systematic immunological insights and suggesting ICs as a potential therapeutic target in HBV treatment.