B7-H1分子对乙肝患者树突状细胞刺激T细胞能力的影响

EFFECT OF B7-H1 ON T-CELL STIMULATING CAPACITY OF DENDRITIC CELLS IN PATIENTS WITH CHRONIC HEPATITIS B INFECTION

目的探讨慢性乙肝患者髓系树突细胞(DCs)表面B7-H1分子在树突细胞介导T细胞免疫应答中的作用。方法受试对象包括46例慢性乙肝患者(11名免疫耐受患者和35名免疫活化患者)和28名健康对照。取外周血,采用流式细胞术检测DCs上B7-H1的表达水平;〔3H〕-TdR掺入试验检测DCs对T淋巴细胞的促增殖效应;ELISA测定混合淋巴细胞培养上清中IFN-γI、L-2I、L-12及IL-10的浓度。结果免疫耐受和免疫活化患者外周血DCs上B7-H1阳性表达率〔(2.21±0.32)%(、7.88±1.40)%〕明显高于健康对照〔(0.35±0.10)%,P<0.01〕。慢性乙肝患者DCs刺激异体T淋巴细胞增殖及产生Ⅰ型细胞因子的能力明显降低,阻断B7-H1共刺激信号途径能够增强患者DCs对T细胞的协同刺激能力。结论慢性乙肝患者外周血DCs上B7-H1表达水平的升高,是导致DCs刺激T淋巴细胞能力下降的一个重要原因。

Objective： To examine the expression of B7-homolog 1（B7-H1） on circulating myeloid dendritic cells（DCs） in patients with chronic hepatitis B virus（HBV） infection and explore its effect on T-cell stimulating capacity of DCs.Methods： The expression of B7-H1 on DCs isolated from forty-six patients with chronic HBV infection,including 11 immune tolerance patients and 35 immune activation patients,and 28 healthy individuals,was determined by FACS（fluorescence-activated cell sorter） gated on Lin1-CD11c＋HLA-DR^＋ cells.（^3H）-TdR incorporation assay was used to determine proliferation of heterologous T cells stimulated by DCs in mixed lymphocytes reaction（MLR）.Concentrations of IFN-γ,IL-2,IL12 and IL-10 in the mixed lymphocytes culture supernatants were examined by ELISA.Results： The positive expression rates in immune tolerance patients,and immune activation patients（（2.21±0.32） %,（7.88±1.40）% respectively）were significantly higher than that in healthy subjects（（0.35±0.10）%,P〈0.01）.The proliferation of heterologous T cells and production of type 1 cytokine stimulated by DCs from patients were significantly decreased.Blockade of B7-H1 on DCs could restore poor T-cell stimulating capacity of DCs.Conclusion： Upregulation of B7-H1 on DCs in patients with hepatitis B virus infection leads to decrease in T-cell stimulating capacity of DCs.