Natural killer cell promotes the HBV clearance via secreting IFN-γ / 安徽医科大学学报

ABSTRACT

Objective To investigate the mechanism of NK cell in eliminating the Hepatitis B virus during HBV in-fection . Methods Acute HBV infection model was established by injecting adult mice hydrodynamically with 20μg of pGEM4Z/HBV1. 2 plasmid. This model was evaluated by detecting serum level of HBsAg and HBcAg in liver tis-sue at the indicated time points by radioimmunoassay and immunohistochemistry respectively. The variation of fre-quency and absolute number of NK cell was analyzed between wide type ( WT ) mice and HBV plasmid-injected mice. Furthermore, the activation and the IFN-γproduction of NK cell were investigated in these mice by flow cy-tometry. HE staining and alanine transaminase( ALT) dectection were used to observe liver injury. To test whether NK cell and IFN-γwere involved in HBV elimination, we used PK136 antibody to clear NK cell and IFN-γneutral-ization antibody toblock IFN-γeffect. Results After the hydrodynamic injection with 20 μg of pGEM4Z/HBV1.2, the serum level of HBsAg and expression of HBcAg in liver tissue were very high at 1 week, but then decreased gradually. However, these antigens almost became negative at 4 to 5 weeks, which mimic acute HBV infection pa-tients. Compared with NK cell from WT mice, the frequency and absolute number of NK cell increased significantly from HBV mice. Also, the NK cells express higher level of CD69 and produce more IFN-γ. Meanwhile, there was no liver injury in HBV mice. Depletion of NK cell or blocking IFN-γ effect in HBV mice could significantly in-crease the level of HBV related antigens. Conclusion In the mouse model of acute HBV infection, NK cell could promote the HBV elimination through secreting IFN-γ.