Exosomes loading Tapasin enhance T cell immune response by autophagy to inhibit HBV replication

Hepatitis B virus (HBV) specific T cell immune response plays a vital role in viral clearance. Dendritic cell derived exosomes (Dexs) can activate T cell immunity effectively. Tapasin (TPN) is involved in antigen processing and specific immune recognition. In the present study, we elucidated that Dexs loading TPN (TPN-Dexs) could enhance CD8⁺ T cell immune response and inhibit virus replication in HBV transgenic mice. T cell immune response and the ability of inhibiting HBV replication were measured in HBV transgenic mice immunized with TPN-Dexs. Meanwhile, CD8⁺ T cell autophagy and specific T cell immune responses were measured in vitro and vivo, and the mechanisms probably involved in were explored. Purified TPN-Dexs could be taken up into the cytoplasm of DCs and upregulate CD8⁺ T cell autophagy to enhance specific T cell immune response. In addition, TPN-Dexs could increase the expression of AKT and decrease the expression of mTOR in CD8⁺ T cells. Further research confirmed that TPN-Dexs could inhibit virus replication and decrease the expression of HBsAg in the liver of HBV transgenic mice. Nevertheless, those also could elicit mice hepatocytes damage. In conclusion, TPN-Dexs could enhance specific CD8⁺ T cell immune responses via the AKT/mTOR pathway to regulate the autophagy and exert the antiviral effect in HBV transgenic mice.