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HBsAg-specific CD8 + T cells as an indispensable trigger to induce murine hepatocellular carcinoma
Cellular & Molecular Immunology ( IF 21.8 ) Pub Date : 2019-11-25 , DOI: 10.1038/s41423-019-0330-1
Xiaolei Hao 1, 2 , Yongyan Chen 1, 2 , Lu Bai 1, 2 , Haiming Wei 1, 2 , Rui Sun 1, 2 , Zhigang Tian 1, 2
Affiliation  

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.



中文翻译:

HBsAg 特异性 CD8 + T 细胞是诱发鼠肝细胞癌不可或缺的诱因

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。

更新日期:2019-11-26
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