Clinical implications of hepatitis B virus core antigen‐mediated immunopathologic T cell responses in chronic hepatitis B

Hepatitis B virus (HBV) infection significantly impacts Asian populations. The influences of continuous HBV antigen and inflammatory stimulation to T cells in chronic hepatitis B (CHB) remain unclear. In this study, we first conducted bioinformatics analysis to assess T‐cell signaling pathways in CHB patients. In a Taiwanese cohort, we examined the phenotypic features of HBVcore‐specific T cells and their correlation with clinical parameters. We used core protein overlapping peptides from the Taiwan prevalent genotype B HBV to investigate the antiviral response and the functional implication of HBV‐specific T cells. In line with Taiwanese dominant HLA‐alleles, we also evaluated ex vivo HBVcore‐specific T cells by pMHC‐tetramers targeting epitopes within HBV core protein. Compared to healthy subjects, we disclosed CD8 T cells from CHB patients had higher activation marker CD38 levels but showed an upregulation in the inhibitory receptor PD‐1. Our parallel study showed HBV‐specific CD8 T cells were more activated with greater PD‐1 expression than CMV‐specific subset and bulk CD8 T cells. Moreover, our longitudinal study demonstrated a correlation between the PD‐1 fluctuation pattern of HBVcore‐specific CD8 T cells and liver inflammation in CHB patients. Our research reveals the HBV core antigen‐mediated immunopathologic profile of CD8 T cells in chronic HBV infection. Our findings suggest the PD‐1 levels of HBVcore‐specific CD8 T cells can be used as a valuable indicator of personal immune response for clinical application in hepatitis management.