T-bet expression in CD8+ T cells associated with chronic hepatitis B virus infection

Abstract

Background: The mechanisms leading to virus-specific CD8+ T cell dysfuction in chronic hepatitis B virus (HBV) infection remain to be elucidated. Our study focused on the role of transcription factor T-bet in HBV infection because it is a crucial regulator of T cell immunity. Methods: We assessed the expression of T-bet along with PD-1, IFN-γ and perforin, in HBV-specific CD8+ T cells from resolved acute hepatitis B (rAHB) patients, chronic hepatitis B (CHB) patients, as well as asymptomatic HBV carriers (ASCs). We observed dynamic changes of T-bet, PD-1, IFN-γ and perforin in acute stage and recovery stage of acute hepatitis B (AHB). Results: Comparing with other cohorts, HBV-specific CD8+ T cells from rAHB demonstrated a superior ability in T-bet, IFN-γ and perforin expression, but an inferior ability in PD-1 expression. In the CHB group, the level of T-bet has a linear relationship with the level of PD-1, IFN-γ and HBV DNA, respectively. A lower expression of T-bet and PD-1 was observed in ASCs when compared with CHB. A higher expression of T-bet, PD-1, IFN-r and perforin was observed in acute stage when compared with the recovery stage of AHB. Conclusions: Our results suggest that expression of T-bet may influence the function of HBV-specific CD8+ T cells and thus can be an attractive target for modulation to improve HBV-specific immunity in CHB.