HBsAg-specific CD8+ T cells as an indispensable trigger to induce murine hepatocellular carcinoma
Xiaolei Hao1,2, Yongyan Chen1,2, Lu Bai1,2
1Division 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.
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.
