HBsAg 特异性 CD8 T 细胞作为诱导小鼠肝细胞癌的不可或缺的触发因素。
HBsAg-specific CD8 T cells as an indispensable trigger to induce murine hepatocellular carcinoma.
机构信息
Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, 230027, Hefei, Anhui, China.
Institute of Immunology, University of Science and Technology of China, 230027, Hefei, Anhui, China.
出版信息
Cell Mol Immunol. 2021 Jan;18(1):128-137. doi: 10.1038/s41423-019-0330-1. Epub 2019 Nov 25.
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 细胞的异常攻击介导的。然而，由于缺乏合适的动物模型，这种免疫发病机制尚未阐明。在这里，我们使用免疫活性 Fah 小鼠作为受体，从 HBs-Tg 小鼠中过继转移 HBsAg 肝细胞来替代受体肝细胞（HBs-HepR）。HBs-HepR 小鼠表现出持续的 HBsAg 表达，伴有慢性肝炎，最终 HCC 的患病率为 100%。产生了 HBsAg 特异性 CD8 T 细胞，其特异性和持续地诱导肝细胞凋亡，并伴有进行性慢性炎症，而 CD8 T 细胞的耗竭或其缺乏可预防 HCC，并且可通过转移 HBsAg 特异性 CD8 T 细胞来重现。综上所述，我们的结果表明 CD8 T 细胞在 HBsAg 驱动的炎症和 HCC 肿瘤发生中起关键作用。
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