HB cAg‐Specific IL ‐21‐Producing CD 4+ T Cells are Associated with Relative Viral Control in Patients with Chronic Hepatitis B

Function exhaustion of specific cytotoxic CD 8+ T cell in chronic virus infection partly results from the low levels of CD 4 help, but the mechanisms by which CD 4 help T cell required to control hepatitis B virus infection are not well understood. In this study, we investigated the role of interleukin‐21‐producing CD 4+ T cell response in viral control of hepatitis B virus infection. HB cAg‐specific interleukin‐21‐producing CD 4+ T cells in blood were detected in patients with hepatitis B virus infection. Patients with acute hepatitis B had greater HB cAg‐specific interleukin‐21‐producing CD 4+ T cells in blood compared with chronic hepatitis B patients, and there was no statistical significance between immune active chronic hepatitis B patients and inactive healthy carrier patients for these cells, whereas frequencies of these cells negatively correlated with HBV DNA levels but positively correlated with HB c18‐27‐specific IFN ‐γ‐producing CD 8+ T cells. Moreover, interleukin‐21 sustained HB c18‐27‐specific CD 8+ T cells in vitro , and interleukin‐21 production by HB cAg‐specific IL ‐21‐producing CD 4+ T cells of acute hepatitis B patients enhanced IFN ‐γ and perforin expression by CD 8+ T cells from chronic hepatitis B patients. Our results demonstrate that HB cAg‐specific interleukin‐21‐producing CD 4+ T cell responses might contribute to viral control by sustaining CD 8+ T cell antiviral function.