中文摘要：

目的 探讨复制缺损型腺病毒载体（Ad）介导异种AFP修饰的树突状细胞（DCs）诱发抗肝癌免疫、打破肿瘤免疫耐受的效果。方法 从HepG2和Hepa 1-6细胞中克隆人和小鼠AFP，插入Ad中构建Ad hAFP和Ad mAFP，用Ad hAFP或Ad mAFP感染小鼠骨髓来源的DC后，在无或有删除CD4或CD8情况下免疫C57BL／6小鼠，7d后取脾细胞行^51Cr释放实验，检测特异性CTL杀伤活性；或给免疫小鼠接种Hepa 1-6肝癌细胞，观察荷瘤小鼠成活情况。结果 Ad hAFP／DCs免疫小鼠1周后其细胞毒性T淋巴细胞杀伤活性明显强于Ad mAFP／DCs。Ad hAFP／DCs免疫小鼠后1周接种5×10^6Hepa 1-6肝瘤细胞，2个月后仍然有80％的小鼠无瘤生长；而接种1×10^6 Hepa 1-6细胞至Ad mAFP／DCs免疫小鼠，2个月后小鼠成活率为20％。删除小鼠CD4或CD8 T细胞均使Ad hAFP/DCs诱发的抗肿瘤免疫反应消失。结论 Ad介导异种AFP修饰的DCs能有效地打破肿瘤的免疫耐受，诱发强烈的抗原特异性细胞免疫反应，这种特异性细胞免疫反应是CD4和CD8依赖性的。

英文摘要：

Objective To investigate the effects of dendritic cells （DCs） infected with adenovirus vector encoding xenogeneic alpha-fetoprotein （AFP） on breaking the immune tolerance and induction of immunity against hepatocellular carcinomas. Methods Human and mouse alpha-fetoprotein full-length cDNA were cloned from human HepG2 and mouse Hepa 1-6 hepatoma cell lines, respectively, using RT-PCR, and then inserted into adenoviral shuttle vectors to construct Ad hAFP and Ad mAFP. Mice were immunized with Ad hAFP-infected DC and in vitro CTL activity against Hepa 1-6 cells was examined by standard^51Cr release assay. Survival was studied of the immunized mice, with or without depletion of CD8 ＋ or CD4 ＋ T cells, inoculated with Hepa 1-6 mouse hepatoma cells. Results The lytic activity of CTL elicited by the Ad hAFP-infected DCs were much stronger than that by Ad mAFP-infected DCs. 80% of the Ad hAFP/DCs-immunized mice of the inoculated with 5 x 10^6 Hepa 1-6 hepatoma cells were still alive two months after inoculation . However, the Ad mAFP/DCs-immunized mice inoculated with 1 × 106 Hepa 1-6 cells were just 20% surviving two months later. Depletion of CD8 ＋ or CD4 ＋ T cells abolished such an antigen-specific immunity elicited by the DCs infected with Ad hAFP. Conclusion Adenovirus vector-mediated xenogeneic AFP-infected DCs can effectively break the immune tolerance to hepatocellular carcinomas in an animal model and induce strong antigen-specific T cell response, which are dependent on CD8 4- and CD4 ＋ T cells.