中文摘要：

目的：探讨腺病毒介导的白细胞介素-18（IL-18）基因转染能否使肿瘤抗原冲击的树突状细胞（dentritic cell,DC）在体外诱导出更强的抗肝癌免疫反应。方法：携IL-18的重组腺病毒载体感染经肝癌细胞株HepG2冻融抗原致敏的DC（AdIL-18-HepG2/DC）,FACS分析AdIL-18-HepG2/DC表面分子的表达,ELISA法检测IL-18的分泌水平,3H-TdR掺入法检测T淋巴细胞增殖能力,MTT法检测细胞毒性T淋巴细胞杀伤效应。结果：AdIL-18-HepG2/DC较未转染DC能高水平地表达CD1a、CD11c、CD80、CD86以及HLA-DR;较未经IL-18转染的DC分泌较高水平的IL-18。AdIL-18-HepG2/DC能非常有效地刺激自体T细胞增殖（CPM值为228 018±1 079）,其刺激强度显著强于AdIL-18DC、HepG2/DC、AdlzcZ/DC及DC（均P〈0.05）。当靶细胞为HepG2时,AdIL-18-HepG2/DC诱导的CTL杀伤活性显著高于其他各组（均P〈0.05）,并且其杀伤能力与效应细胞数量成正比。结论：IL-18基因转染且肝癌抗原致敏的DC可以显著增强DC的特异性抗肝癌效应。

英文摘要：

Objective：To study whether interleukin （IL）-18 can promote tumor antigen-pulsed dendritic cells （DCs） to induce specific CTL against hepatocellular carcinoma（ HCC ） in vitro. Methods： The recombinant adenovirus expression plasmid AdIL-18 was transfected into DCs pulsed by HepG2 lysates （AdlL-18-HepG2/DC）. The surface molecules of AdIL-18-HepG2/DCs were analyzed by flow cytometry. IL-18 levels in culture supernatant of AdIL-18-HepG2/DCs were measured by ELISA. The ability of AdIL-18-HepG2/DC to induce proliferation of autologous T lymphocytes was evaluated by 3H-TdR assay. The in vitro CTL antitumor activity induced by AdIL-18-HepG2/DC on HepG2 cell was detected by MTI＇. Results： IL-18 promoted expression of CDla, CD1 lc, CD80, CD86 and HLA-DR on HepG2/DCs compared with untransfected DCs. AdIL-18-HepG2/DCs secreted more IL-18 in vitro compared with untransfected DCs. AdIL-18- HepG2/DC effectively stimulated proliferation of autologous T cells （ CPM being 228 018 ± 1 079） ; the stimulating effect was significantly higher than those of AdIL-18DC, HepG2/DC, AdlzcZ/DC, and DC （all P 〈 0.05 ）. CTL induced by TAA pulsed/IL-18 modified DC had significantly higher cytotoxicity against HepG2 cells compared with that induced by other DCs. Conclusion： AdIL-18-HepG2/DCs have enhanced ability to induce specific CTL in killing hepatocellular carcinoma HepG2 cell line.