The 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.

病毒抗原 (Ag) 特异性 CD8 ⁺源自多能干细胞(PSC)的细胞毒性T淋巴细胞(CTL)，即PSC-CTL，具有抑制乙型肝炎病毒(HBV)感染的能力。过继转移后，PSC-CTL 可渗入肝脏以抑制 HBV 复制。然而，病毒 Ag 特异性 PSC-CTL 激发抗病毒反应的机制仍有待完全阐明。在这项研究中，我们从诱导的 PSC (iPSC) 生成了功能性 HBV 表面 Ag 特异性 CTL，即 iPSC-CTL，并研究了小鼠模型中 CTL 介导的抗病毒复制的潜在机制。我们表明，HBV 表面 Ag 特异性 iPSC-CTL 的过继转移极大地抑制了 HBV 复制并阻止了 HBV 表面 Ag 表达。我们进一步证明过继转移显着增加了 T 细胞的积累和抗病毒细胞因子的产生。这些结果表明，干细胞衍生的病毒 Ag 特异性 CTL 可以在肝脏中大量积累，并通过产生抗病毒细胞因子来抑制 HBV 复制。