PD-1 blockage reverses immune dysfunction and viral persistence to Hepatitis B virus infection in mouse animal model (67.16)

Abstract

Abstract Recent studies in animal models of virus infection, indicate that the interaction between the inhibitory receptor programmed death (PD)-1 on lymphocytes and its ligands plays a critical role in T-cell exhaustion by inducing T-cell inactivation, and high PD-1 expression levels on peripheral T-lymphocytes as well as the possibility to improve the T-cell function by blocking PD-1-mediated signaling to confirm the importance of this inhibitory pathway in inducing T-cell exhaustion. We studied T-cell exhaustion and the effects of PD-1/PD-L1 blockade on intrahepatic infiltrating T cells in our recently developed mouse model of hepatitis B virus (HBV) persistence with hydrodynamic injection of HBV DNA. In this mouse animal model, we demonstrated that there were increased intrahepatic PD-1 expressing CD8+ T cells and increased CD4+ FoxP3+ T cells in the mice with HBV persistence. Blockade of PD-1/PD-L1 interaction increased HBcAg-specific IFN-gamma production in intrahepatic T lymphocytes. Furthermore, blocking the interaction of PD-1 with its ligand PD-L1 by anti-PD-1 mAb reversed the viral persistence to clearance of HBV viral constructs in vivo. Our results indicated that PD-1 blockage reverses immune dysfunction and viral persistence to HBV infection in mouse animal model, suggesting anti-PD-1 mAb might be a good therapeutic candidate for chronic HBV infection.