Fusion protein of tapasin and hepatitis B core antigen 18-27 enhances T helper cell type 1/2 cytokine ratio and antiviral immunity by inhibiting suppressors of cytokine signaling family members 1/3 in hepatitis B virus transgenic mice

摘要

Persistent hepatitis B virus (HBV) infection is characterized by a weak adaptive immune response, which is considered to be due to an imbalance of T helper cell types 1 and 2 (Th1/Th2). Suppressors of cytokine signaling (SOCS) family members, particularly SOCS1 and SOCS3, have been demonstrated to be important in the regulation of T cell differentiation. Previous studies by our group showed that the expressed and purified fusion protein of cytoplasmic transduction peptide (CTP) and HBV core antigen 18-27 (HBcAg18-27)-tapasin was able to enter the cytoplasm of bone marrow-derived dendritic cells (BMDCs), promoting the maturation of BMDCs and efficiently enhancing T cell immune responses in vitro. In the present study, HBcAg-specific immune responses induced by CTP-HBcAg18-27-tapasin in HBV were assessed in transgenic mice, and SOCS1 and SOCS3 were identified as negative regulators of this response. The Th1/Th2 cytokine ratio was analyzed by ELISA. The expression of T cell-specific T-box transcription factor (T-bet) and GATA-binding protein 3 (GATA-3), SOCS1 and SOCS3 were detected by real-time quantitative polymerase chain reaction and western blot analysis. The results demonstrated that CTP-HBcAg18-27-tapasin significantly increased the Th1/Th2 cytokine ratio in HBV transgenic mice. CTP-HBcAg18-27-tapasin immunization more efficiently suppressed the expression of serum hepatitis B surface antigen (HBsAg), HBV DNA as well as liver HBsAg and HBcAg in HBV transgenic mice. Furthermore, CTP-HBcAg18-27-tapasin promotes T-bet but reduces GATA-3 expression. In addition, the expression of SOCS1 and SOCS3 was significantly downregulated in the CTP-HBcAg18-27-tapasin group compared with the control groups. In conclusion, the present study demonstrated that CTP-HBcAg18-27-tapasin enhanced the Th1/Th2 cytokine ratio and antiviral immunity by suppressing SOCS1/3 in HBV transgenic mice.