HCV C-Fc融合基因修饰的树突状细胞疫苗抗HCV功能研究

HCV C-Fc engineered mice dendritic cells enhance immune response against HCV

目的 探讨丙型肝炎病毒 (HCV)C Fc基因修饰的树突状细胞 (DCs)能否诱导抗HCV细胞和体液免疫反应。方法 将pcDNA3 HCV Fc质粒用电穿孔法转染经过白介素 4 (IL 4 ) ,粒 巨噬细胞集落刺激因子 (GM CSF)刺激增殖的小鼠DCs前体细胞 ,观察HCV、Fc抗原表达 ;将制备的 5×10 5/ 10 0 μlDC疫苗皮下免疫Balb/c小鼠 ,两周后检测特异性抗体、脾脏CD4 +、CD8+细胞增殖作用以及诱导的细胞毒性T淋巴细胞 (CTL)反应。结果 HCVC Fc基因电穿孔法转染细胞在上述细胞因子作用下发育成能有效表达HCVC Fc并具有典型形态学与表型特征的DCs。免疫小鼠后 ,HCVC Fc基因转染DCs能诱导产生抗HCV特异性抗体和较强的CTL反应。结论 HCVC Fc基因修饰的DCs能增强对HCV特异性CTL效应的诱导能力 。

Objective To explore whether HCV C Fc engineered mice dendritic cells (DCs) might enhance its antigen presenting functions to augment cell mediated immune responses. Methods The early replicating progenitors of DCs (stimulated by IL 4 and GM CSF) were transfected with HCV C Fc recombinant vector by electro transfection. 5×10 5/100 μl HCV C Fc transfected and untransfected DCs were injected into mice subcutaneously. Two weeks later, specific Th and CTL immune responses were dedected. Results After culturing in the cocktail of the above mentioned cytokines, HCV C Fc transfected DCs developed and maintained the characteristic morphological and phenotypic features of DCs. The HCV C Fc transfected DCs stimulated the autologous lymphocytes to proliferate to a higher level, and the specific CTL response was enhanced when compared with the effects shown in untransfected DCs. Meanwhile, the production of anti HCV was observered in transfected DCs group. Conclusions HCV C Fc engineered human dendritic cells enhanced the functions to stimulate Th1 cells as well as to induce specific CTL effect, showing its promise future for developing anti viral vaccine.