CD8low T-cell subpopulation is increased in patients with chronic hepatitis B virus infection

•CD8low T cells were significantly more frequent in the chronic HBV patients.•Frequency of CD8low T cells shows a positive relationship with levels of plasma soluble HLA class I molecules.•CD8low T cells in chronic HBV patients display higher levels of Tc2-polarized and suppressive markers.•CD8low T-cell frequency is negatively associated with HBc-specific CD8+ responses in the chronically HBV infected patients. Recent studies suggest that CD8+ T cells with down-regulated CD8 expression (CD3+CD8low T cells) represented as a distinct phenotype of CD8+ T cells are increased and linked to disease severity in some chronically persistent infection, such as chronic HIV and parasite infection. However, the role of CD3+CD8low T cells in the context of chronic HBV infection is poorly understood. In this study, peripheral blood samples of 47 chronic hepatitis B patients and 19 healthy controls were collected and tested for the frequency and phenotype of CD8low T cells. The circulating CD8low T cells were significantly more frequent in the patients compared to those in healthy controls, and the CD8low T cells in the patients expressed less IFN-γ and more mTGF-β1 than those in the controls, suggesting their type-2 polarized and suppressive properties. Meanwhile, the concentrations of plasma soluble HLA class I molecules were found elevated in the patients, and positively associated with the frequencies of CD8low T cells. Furthermore, the CD8low T-cell frequency in the HLA-A2-positive patients (n=21) was found negatively correlated with the T-cell responsiveness against the HBc18–27 peptide, the latter was impaired as revealed by IFN-γ Elispot assay. Our findings suggested that a better understanding of the involvement of CD8low T cells in chronically persistent HBV infection would add to our knowledge of the impaired T-cell response in the patients.