Kinetics of peripheral hepatitis B virus-specific CD8+ T cells in patients with onset of viral reactivation

Patients with resolved hepatitis B virus (HBV) infection undergoing chemotherapy or immunosuppressive therapy are potentially at risk of HBV reactivation. However, it remains unclear how liver disease develops after HBV reactivation. To compare the host immune response against HBV, we performed immunological analyses of six HBV reactivation patients. The numbers of peripheral HBV-specific CD8(+) T cells were investigated longitudinally in six HLA-A2- and/or A24-positive patients with HBV reactivation. In addition, 34 patients with resolved HBV, 17 patients with inactive chronic hepatitis B (ICHB), 17 patients with chronic hepatitis B (CHB) and 12 healthy controls were analyzed. The number and function of HBV-specific CD8(+) T cells were assessed by flow cytometry using tetramer staining and intracellular IFN-gamma production. Furthermore, the numbers of CD4(+)CD25(+) or CD4(+)Foxp3(+) T cells and serum inflammatory cytokine levels were analyzed. The frequency of HBV-specific CD8(+) T cells was significantly increased in HBV reactivation patients compared with ICHB and CHB patients. In addition, the number of HBV-specific CD8(+) T cells was increased in resolved HBV patients compared with ICHB patients. PD-1 expression was decreased in HBV reactivation patients compared with ICHB and CHB patients. The numbers of HBV-specific CD8(+) T cells and CD4(+)CD25(+) or CD4(+)Foxp3(+) T cells were negatively correlated following onset of HBV reactivation. During HBV reactivation, the frequency of HBV-specific CD8(+) T cells increased even though the administration of immunosuppressive drugs and interactions with CD4(+) regulatory T cells may be important for the onset of liver disease.