Recent studies suggest that CD8(+) T cells with down-regulated CD8 expression (CD3(+)CD8(low) 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(+)CD8(low) 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 CD8(low) T cells. The circulating CD8(low) T cells were significantly more frequent in the patients compared to those in healthy controls, and the CD8(low) T cells in the patients expressed less IFN-gamma and more mTGF-beta 1 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 CD8(low) T cells. Furthermore, the CD8(low) T-cell frequency in the HLA-A2-positive patients (n = 21) was found negatively correlated with the T-cell responsiveness against the HBc(18-27) peptide, the latter was impaired as revealed by IFN-gamma Elispot assay. Our findings suggested that a better understanding of the involvement of CD8(low) T cells in chronically persistent HBV infection would add to our knowledge of the impaired T-cell response in the patients. (C) 2013 Elsevier Ltd. All rights reserved.