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.