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

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.

SUBMITTER: Hao X 

PROVIDER: S-EPMC7853119 | biostudies-literature |

REPOSITORIES: biostudies-literature