无症状乙型肝炎病毒携带者外周血单个核细胞分泌细胞因子的研究

Study on the cytokines induced from PBMCs of asymptomatic HBV carriers

目的通过分析乙型肝炎病毒无症状携带者外周血单个核细胞(peripheral blood mononuclear cells,PBMCs)分泌的细胞因子,探索乙肝病毒慢性感染的病理机制。方法用不同的抗原物质及抗体刺激培养肝炎病毒无症状携带者PBMCs,ELISA检测细胞培养上清中不同的细胞因子水平。结果HBV携带者PBMCs细胞分泌的IFN-γ、IL-12明显比健康对照组减少,而TGF-β和IL-10等细胞因子的水平则明显升高;用抗体同时中和TGF-β和IL-10才能恢复IFN-γ的表达水平,而低剂量的外源性IL-12协同乙肝抗原能促进PBMCs抗原特异性T细胞分泌IFN-γ。结论PBMCs分泌IL-12减少可能是乙肝病毒携带者长期带毒的根本原因,联合使用IL-12和乙肝特异性抗原可促进乙肝病毒携带者PBMCs的细胞免疫功能。

Objective To investigate the cellular immune state and pathological mechanism of HBV chronic infection by analyzing the cytokines produced by peripheral blood mononuclear cells （PBMCs） of asymptomatic HBV carriers. Methods PBMCs were prepared from diagnosed chronic asymptomatic HBV individuals and cultured in the presence of different antigens and antibodies. The levels of IFN-γ, IL-12, TNF-α ,TGF-β and IL-10 in the culture supernatants were respectively detected by ELISA. Results The levels of IFN-γ, IL-12 were significantly lower than in the counterparts from healthy controls; meanwhile, those of TGF-β and IL-10 were elevated markedly. Neutralization of TGF-β and IL-10 simultaneously restore the IFN-γ production from PBMCs of HBV carriers, and exogenous IL-12 in low dose combined with specific HBV antigens promoted IFN-γ production. Conclusion Reduction of IL-12 from PBMCs may be the fundamental reason of viral persistence in HBV chronic carriers, combined IL-12 and specific HBV antigen promoted the celluar immunity of PBMCs from HBV carriers.