IL-4基因修饰增强脑胶质瘤细胞毒性T淋巴细胞杀伤活性机制的探讨  

Enhancing killing activities of glioma cell specific cytotoxical T lymphocyte by IL-4 gene modification

作　　者：李成荣[1] 付劲蓉[1] 

机构地区：[1]深圳市儿童医院分子免疫研究室,518026

出　　处：《中华儿科杂志》2002年第6期333-336,共4页Chinese Journal of Pediatrics

基　　金：国家自然科学基金资助 ( 394 70 733) ;深圳市卫生系统科研基金资助 (19994 0 0 6 )

摘　　要：目的　进一步探讨白细胞介素 4(IL 4)基因修饰瘤苗增强细胞毒性T淋巴细胞 (CTL)杀伤活性的机制。方法　通过逆转录病毒载体PL IL 4 SN将人IL 4基因导入神经胶质瘤系SHG44细胞 ,以IL 4基因修饰瘤苗和野生型瘤细胞作刺激细胞诱导CTL反应 ,通过流式细胞仪检查瘤细胞表面分子的表达。结果　 (1 )IL 4基因修饰诱导瘤细胞表达MHC Ⅱ类抗原、B7 1及ICAM 1等免疫刺激分子 ,对MHC I类抗原表达无影响 ,其瘤苗诱导的CTL杀伤活性为野生型瘤细胞的 7倍 (P <0 0 1 )。(2 )加入抗IL 4单抗可完全阻断IL 4诱导的细胞表面分子的表达 ,IL 4基因修饰瘤苗诱导CTL反应时培养上清可检测到大量IL 2的产生。抗IL 4或抗细胞表面分子单抗可降低IL 2产生及抑制CTL反应。结论　IL 4基因修饰可能是通过诱导MHC Ⅱ类抗原等表面分子表达 ,促进ILObjective To further explore the mechanism enhancing killing activities of tumor cell specific cytotoxical T lymphocyte (CTL) by IL 4 gene modification Methods IL 4 gene was introduced into SHG44 cells of the human glioma cell line by using the retroviral vector PL IL 4 SN The wild SHG44 and IL 4 gene modified tumor cells were used to induce CTL responses, and cellular surface molecules were detected with the flow cytometry Results The killing activities of tumor cell specific CTL in IL 4 gene modified groups increased from 10 4% to 76 5%, which was about seven fold higher than CTL killing activities induced by wild SHG44 cells ( P <0 01) The high expression levels of MHC class Ⅱ antigens, the costimulatory molecules B7 1 and adherent molecules ICAM 1 were found in IL 4 gene transferred tumor cells The expression of MHC class Ⅰ was not affected by IL 4 gene modified tumor vaccines, and was completely abrogated by using the anti IL 4 monoclonal antibody A significant increase of IL 2 secretion was detected during the induction of CTL responses when IL 4 gene modified tumor cells were used as stimulatory cells The IL 2 secretion and CTL responses were inhibited by using anti IL 4 or anti surface molecule monoclonal antibodies Conclusion IL 4 gene modification might enhance tumor cell specific CTL killing activities through the induction of the cellular surface molecules expression and the facilitation of IL 2 secretion

关 键 词：脑胶质瘤 白细胞介素4 T淋巴细胞 细胞毒性 基因修饰瘤苗 基因治疗 

分 类 号：R730.3[医药卫生—肿瘤]