摘要：SummaryThe viral antigen (Ag)-specific CD8+cytotoxic T lymphocytes (CTLs) derived from pluripotent stem cells (PSCs), i.e., PSC-CTLs, have the ability to suppress hepatitis B virus (HBV) infection. After adoptive transfer, PSC-CTLs can infiltrate into the liver to suppress HBV replication. Nevertheless, the mechanisms by which the viral Ag-specific PSC-CTLs provoke the antiviral response remain to be fully elucidated. In this study, we generated the functional HBV surface Ag-specific CTLs from the induced PSC (iPSCs), i.e., iPSC-CTLs, and investigated the underlying mechanisms of the CTL-mediated antiviral replication in a murine model. We show that adoptive transfer of HBV surface Ag-specific iPSC-CTLs greatly suppressed HBV replication and prevented HBV surface Ag expression. We further demonstrate that the adoptive transfer significantly increased T cell accumulation and production of antiviral cytokines. These results indicate that stem cell-derived viral Ag-specific CTLs can robustly accumulate in the liver and suppress HBV replication through producing antiviral cytokines.Graphical AbstractDisplay OmittedHighlights•Generation of functional viral Ag-specific CTLs from iPSCs, i.e., iPSC-CTLs•Viral Ag-specific iPSC-CTLs suppress HBV replication in a murine model•Adoptive transfer of viral Ag-specific iPSC-CTLs generates persistent α-HBV T cells•Adoptive transfer of viral Ag-specific iPSC-CTLs produces antiviral IFN-γ and TNF-⍺Immunology; Functional Aspects of Cell Biology
