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

• Published in: Journal of medical virology 2023-04, Vol.95 (4), p.e28746-n/a
• Main Authors: Lv, Mengjiao, Yao, Ting, Zhang, Yi, Ma, Siyuan, Chen, Jinmei, Tang, Zhenghao, Zang, Guoqing, Chen, Xiaohua
• Format: Article
• Language: English
• Subjects: AKT protein; Animals; Antigen Presentation; Antigen processing; Antigens; Autophagy; CD8 antigen; CD8-Positive T-Lymphocytes; Cytoplasm; dendritic cell derived exosomes; Dendritic cells; Exosomes; HBV; Hepatitis B; Hepatitis B surface antigen; Hepatitis B virus; Hepatocytes; Immune clearance; Immune response; Immune response (cell-mediated); Immune system; Immunization; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred C57BL; Mice, Transgenic; Proto-Oncogene Proteins c-akt; Replication; T cell immune response; Tapasin; TOR protein; TOR Serine-Threonine Kinases; Transgenic animals; Transgenic mice; Virology; Viruses
• ISSN: 0146-6615; 1096-9071
• DOI: 10.1002/jmv.28746

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.