Patients with acute hepatitis B had greater HBcAg-specific interleukin-21-producing CD4+ 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 HBc18-27-specific IFN-γ-producing CD8+ T cells. Moreover, interleukin-21 sustained HBc18-27-specific CD8+ T cells in vitro, and interleukin-21 production by HBcAg-specific MK-8669 IL-21-producing CD4+ T cells of acute hepatitis B patients enhanced IFN-γ and perforin expression by CD8+ T cells from chronic hepatitis B patients. Our results demonstrate that HBcAg-specific interleukin-21-producing CD4+ T cell responses might contribute to viral control by sustaining CD8+

T cell antiviral function. The quantity and quality of adaptive antiviral immune response influences clinical outcome of infection by the non-cytopathic, hepatotropic hepatitis B virus (HBV) [1]. The multispecific and vigorous CD4+ T cell and CD8+ T cell reactivity was present in acute HBV-infected patients who succeed in clearing HBV infection. However, in SB203580 solubility dmso chronic HBV infection, the immune responses are weak and oligoclonal. The HBV-specific cytotoxic CD8+ T cells, which are believed to play a crucial role in viral clearance, show exhausted antiviral function Clomifene characterized by an inability to produce cytokines such as IFN-γ and TNF-α, low cytotoxic activities or low proliferation in response to cognate antigen [2]. Studies in other persistent virus infection have shown that exhaustion of specific cytotoxic CD8+ T cell response mainly result from the high levels of virus antigen and low levels of CD4 help T cell[3]. Indeed, virus-specific CD4+ T cell responses are required for the efficient development of effector-specific cytotoxic CD8 T cell and B cell antibody production particularly during chronic HBV infection [4, 5]. A recent study showed that early activation

of CD4+ T cells correlates with an influx of HBV-specific CD8+ T cells into the liver in a chimpanzee model of acute HBV infection, and animals depleted of CD4+ T cells become persistently infected when inoculated with a dose of HBV [6, 7]. These data indicate that virus-specific CD4+ T cell subsets play a critical role in determining immune responses to the virus and disease outcome. However, the mechanisms by which CD4 help T cell required to control HBV infection are not well understood. Recently, several studies in animal model of LCMV infection demonstrate that interleukin-21 (IL-21), a common γ-chain cytokine, is essential for sustained specific CD8+ T cell response and control of viraemia in persistent viral infection [8-10].