IL-12 promotes HBV-specific central memory CD8+ T cell responses by PBMCs from chronic hepatitis B virus carriers

It is very important to understand the mechanism of immune tolerance or hyporesponsiveriess in hepatitis B virus (HBV) infected individuals so as to treat HBV. In the present study we detected the cellular immune states of chronic asymptomatic HBV carriers and tried to probe their mechanisms and the strategy to promote their specific cellular immune responses. HBV nonspecific antigens and specific antigens alone or with IL-12 were used to stimulate peripheral blood mononuclear cells (PBMCs) from the HBV carriers and healthy controls for evaluation of cytokine responses. IFN-gamma, TNF-alpha, IL-12P40 and IL-12P70 in the supernatants were assayed by ELISA, and the frequency as well as phenotype of IFN-gamma-producing cells were detected by ELISpot and FACS, respectively. The results showed that PBMCs from the HBV carriers secreted less IFN-gamma and IL-12 than those from the healthy controls. Exogenous IL-12 in combination with HBV specific antigens promoted PBMCs from the HBV carriers to secret more IFN-gamma by augmenting the frequency of CD8(+) IFN-gamma(+) T cells. Further studies indicated that majority of IFN-gamma-producing cells belonged to central memory CD8+ T cells. Thus, our study provided the evidence that insufficient production of IL-12 is involved in the mechanism of hyporesponsiveness in HBV infected persons. The addition of IL-12 plus HBV specific antigen into cultures of PBMCs could restore their specific cellular immune responses. These data may have an important implication in the possibility of designing effective vaccine against HBV infection. (c) 2006 Elsevier B.V. All rights reserved.