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HBsAg-specific CD8+ T cells as an indispensable trigger to induce murine hepatocellular carcinoma

Cellular & Molecular Immunology volume 18, pages 128–137 (2021)Cite this article

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Abstract

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.

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Data availability

Raw sequencing data have been deposited in GEO Datasets with the GEO accession number GSE130880.

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Acknowledgements

We thank Dr. Zhexiong Lian for providing the CD8 KO mice and Dr. Xin Wang for providing the Fah KO mice. We thank the NIH tetramer core facility for kindly providing HBsAg-Tetramer used in this study. This work was supported by the Chinese Academy of Science (XDB29030201), the National Key R&D Program of China (2018YFA0507403, 2017ZX10202203-009-002), and the Natural Science Foundation of China (#81788101, 81671554, 91542000, 81821001).

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Authors and Affiliations

  1. 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

    Xiaolei Hao, Yongyan Chen, Lu Bai, Haiming Wei, Rui Sun & Zhigang Tian

  2. Institute of Immunology, University of Science and Technology of China, 230027, Hefei, Anhui, China

    Xiaolei Hao, Yongyan Chen, Lu Bai, Haiming Wei, Rui Sun & Zhigang Tian

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  1. Xiaolei Hao
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Contributions

X.H., Y.C., L.B., R.S., and Z.T. initiated and designed the research. X.H., Y.C., R.S., and Z.T. wrote the manuscript. X.H. and L.B. performed all the experiments and analyzed and interpreted the results. H.W. contributed to the discussion of the results.

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Correspondence to Rui Sun or Zhigang Tian.

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Hao, X., Chen, Y., Bai, L. et al. HBsAg-specific CD8+ T cells as an indispensable trigger to induce murine hepatocellular carcinoma. Cell Mol Immunol 18, 128–137 (2021). https://doi.org/10.1038/s41423-019-0330-1

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