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。

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 (AdIL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 MTT. Results: IL18 promoted expression of CD1a, CD11c, 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.

国家自然科学基金资助项目（No.30672391）；全军医药卫生科研资助项目基金(No.06MA205)； 陕西省自然科学基金资助项目（No.2004C222）