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

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.