Hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC) is mediated by an inappropriate attack by HBV-specific T cells in patients. However, this immunopathogenic process has not been clarified because of the lack of a suitable animal model. Here, we used immunocompetent Fah^−/− mice as the recipients in the adoptive transfer of HBsAg⁺ hepatocytes from HBs-Tg mice to replace the recipient hepatocytes (HBs-HepR). HBs-HepR mice exhibited persistent HBsAg expression with chronic hepatitis and eventually developed HCC with a prevalence of 100%. HBsAg-specific CD8⁺ T cells were generated and specifically and continuously induced hepatocyte apoptosis with progressive chronic inflammation, and the depletion of CD8⁺ T cells or their deficiency prevented HCC, which could then be reproduced by the transfer of HBsAg-specific CD8⁺ T cells. In summary, our results demonstrated that CD8⁺ T cells plays a critical role in HBsAg-driven inflammtion and HCC tumorigenesis.

乙型肝炎病毒 (HBV) 相关的肝细胞癌 (HCC) 是由患者体内 HBV 特异性 T 细胞的不当攻击介导的。然而，由于缺乏合适的动物模型，这种免疫致病过程尚未阐明。在这里，我们使用免疫活性 Fah ^-/-小鼠作为接受者，将 HBsAg ⁺肝细胞从 HBs-Tg 小鼠过继转移以替代接受者肝细胞 (HBs-HepR)。HBs-HepR 小鼠在慢性肝炎中表现出持续的 HBsAg 表达，并最终以 100% 的患病率发展为 HCC。产生 HBsAg 特异性 CD8 ⁺ T 细胞，特异性持续诱导肝细胞凋亡，伴随进行性慢性炎症，CD8 ⁺耗竭T 细胞或其缺陷阻止了 HCC，然后可以通过转移 HBsAg 特异性 CD8 ⁺ T 细胞来复制 HCC 。总之，我们的结果表明 CD8 ⁺ T 细胞在 HBsAg 驱动的炎症和 HCC 肿瘤发生中起着关键作用。