The role of cytotoxic T cells and cytokines in the control of hepatitis B virus infection.

The aim of this study was to elucidate the molecular basis for viral clearance and liver disease in the pathogenesis of hepatitis B virus (HBV) infection. Using transgenic mice that replicate HBV at high levels in the liver as recipients of HBV-specific cytotoxic T cells (CTL), we have shown that the antiviral potential of the CTL is primarily mediated by noncytolytic mechanisms that involve the intra-hepatic production of IFN-gamma by these cells. We also showed that, following antigen recognition, HBV-specific CTL recruit antigen non-specific inflammatory cells that contribute to amplify the liver disease initiated by CTL. These results provided insight into immunological and virological processes that may lead to the development of new therapeutic strategies to terminate chronic HBV infection.