Interleukin-21 responses in patients with chronic hepatitis B.

Interleukin (IL)-21 has been demonstrated to play a pivotal role in controlling chronic viral infections. However, little is known about the regulatory role of IL-21 in T cell immunity during the process of chronic hepatitis B (CHB). In the present study, the levels of serum IL-21 in 77 patients with various degrees of CHB in immune clearance phase (IC), 25 patients infected with hepatitis B virus (HBV) in immune tolerance phase (IT), and 25 healthy controls (HC) were measured and their potential association with major clinic indexes was examined. Peripheral blood mononuclear cells from CHB patients were stimulated with hepatitis B core antigen (HBcAg) in the presence or absence of anti-IL-21 antibody or recombinant IL-21, and the frequency of HBcAg-specific IL-21(+)CD4(+) and interferon (IFN)-γ(+)CD8(+) T cells was characterized by flow cytometry. Our data indicated that the levels of serum IL-21 were significantly higher in the IC CHB patients than that in the other groups and were positively correlated with the levels of serum HBV DNA and HBeAg in the IC patients. There was a low frequency of HBcAg-specific IL-21(+)CD4(+) T cells in IC CHB patients. Further, IL-21 enhanced HBcAg-specific IFN-γ(+)CD8(+) T cell proliferation, while treatment with anti-IL-21 inhibited antigen-specific IFN-γ(+)CD8(+) T cell expansion in vitro. Our findings imply that IL-21 positively regulates proinflammatory IFN-γ(+)CD8(+) T cell responses during the process of chronic HBV infection in humans.