Frequencies and characterization of HBV-specific cytotoxic T lymphocytes in self-limited and chronic hepatitis B viral infection in China

Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) are believed to play a major role in viral clearance and disease pathogenesis during HBV infection. To clarify the differences in host immune responses between self-limited and chronic HBV infections, we constructed three HLA-A*0201/HBV tetramers with immunodominant epitopes of core18–27, polymerase 575–583 and envelope 335–343, and analyzed the HBV-specific CTLs in peripheral blood mononuclear cells (PBMCs) from patients infected with HBV. The frequencies and expansion ability of HBV-specific CD8+ T cells in most self-limited HBV infected individuals were higher than those in chronic HBV-infected patients. HBV-specific CD8+ T cells could be induced by in vitro peptide stimulation from chronic patients with a low level of serum HBV-DNA but not from those with a high level of serum HBV-DNA. In chronic infection, no significant correlation was found either between the frequencies of HBV-specific CD8+ T cells and the viral load, or between the frequencies and the levels of alanine transaminase. Our results suggested that the frequencies of HBV-specific CTLs are not the main determinant of immune-mediated protection in chronic HBV infection and immunotherapeutic approaches should be aimed at not only boosting a HBV-specific CD8+ T response but also improving its function.