Hepatitis B e-antigen Persistency is Associated with the Properties of HBV-Specific CD8 T Cells in CHB Patients

To investigate the correlation between the HBeAg and the properties of HBV-specific CD8 T cells, as well as liver injury, serum HBV markers, liver histology, the frequency and phenotypic characteristics of CD4(+)CD25(+) Treg and HBV-pentamer(+) CD8 T cells were measured. No significant differences between the median serum ALT levels, the frequency and Foxp3 expression of CD4(+)CD25(+) Treg, and liver fibrosis were observed. Higher HBV DNA levels in HBeAg+ patients were observed, while liver necroinflammation was more severe in HBeAg- patients. Differences in HBV-pentamer(+) T cell frequency were not significant, but increased PD-1 and CTLA-4 expression on HBV-specific CD8 T cells was seen in the HBeAg+ group. HBV-peptide stimulation with anti-PD-L1 and anti-CTLA-4 significantly increased the proliferation in PBMCs from both groups, but enhanced IFN-gamma production only in the HBeAg+ patients. Therefore, HBeAg persistency in CHB patients probably increased the expression of PD-1 and CTLA-4 on HBV-specific CD8 T cells, which may be associated with the low intensity of T cell responses and high HBV DNA load.