HBcAg induces interleukin-10 production, inhibiting HBcAg-specific Th17 responses in chronic hepatitis B patients.

T-helper (Th) 17 cells have been shown to have an important role in host defense against viral infection. However, little is known about the regulation of Th17 cells in hepatitis B virus (HBV) infections. Peripheral blood mononuclear cells (PBMCs) isolated from patients with chronic hepatitis B (CHB) were stimulated with anti-interleukin (IL)-10 antibody or recombinant IL-10. The frequency of hepatitis B core antigen (HBcAg)-specific Th17 cells was characterized and produced cytokines were determined by flow cytometry. A low frequency of Th17 cells and a high frequency of Th1 cells were detected in CHB patients. HBcAg stimulation promoted IL-17A, IL-22, IL-23, IL-6, transforming growth factor (TGF)-β and IL-10 production by PBMCs from CHB patients, but not from healthy controls. Furthermore, endogenous IL-10 inhibited HBcAg-stimulated production of IL-17A, IL-22, IL-6 and IL-23, but not TGF-β. Treatment with IL-10 inhibited the HBcAg-stimulated activation of Th17 cells, whereas anti-IL-10 antibody significantly increased the frequency of Th17 and Th1 cells, but not that of CD4(+)CD25(+) regulatory T cells, associated with upregulating RORγt expression in CD4(+) T cells. HBcAg stimulated the production of IL-10, which negatively regulated HBcAg-specific Th17 cell responses in CHB patients. Our findings may represent one evasion strategy for HBV to subvert specific antiviral responses in humans.