摘要
目的 进一步探讨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基因导入白血病细胞系HL 6 0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肿瘤细胞表面MHC Ⅰ、MHC Ⅱ类抗原及B7 1、ZCAM 1等分子表达。结果 IL 4基因修饰诱导瘤细胞表达MHC Ⅱ类抗原、B7 1及ICAM 1等细胞表面分子 ,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) ,加入抗IL 4单抗可完全阻断IL 4诱导的细胞表面MHC Ⅱ类抗原及B7 1、ICAM 1分子的表达 ,IL 4基因修饰瘤苗诱导CTL反应时培养上清可测及IL 2产生。抗IL 4或抗细胞MHC Ⅱ类抗原等表面分子单抗可降低IL 2产生及抑制CTL反应。结论 诱导MHC Ⅱ类抗原等表面分子表达 ,促进IL 2产生 ,可能是IL 4基因修饰增强CTL杀伤活性的作用机制之一。
Objective To explore the mechanism of enhancing killing activity of tumor cell specific cytotoxic T lymphocyte (CTL) by IL 4 gene modified tumor cells (IL 4mTC). Methods IL 4 gene was introduced into HL 60 cells through retroviral vector PL IL 4 SN. Wild and IL 4 mTC were used to induce CTL responses, and cell surface molecules were assayed by flow cytometry. Results The killing activity of tumor cell specific CTL in IL 4 mTC group was increased from 11.8% to 77.2%, about sevenfold higher than that induced by wild HL 60 cells (P<0.01). High level expression of MHC class Ⅱ antigens as well as B7 1 and ICAM 1 molecules was observed in IL 4 mTC. The expression of MHC class I antigen was not affected by IL 4 gene modification. The expression of cell surface molecules induced by IL 4 mTC was completely abrogated by anti IL 4 McAb. A significant increase of IL 2 secretions was detected during IL 4 mTC inducing CTL responses. IL 2 secretion and CTL response were inhibited by anti IL 4 or anti surface molecule McAbs. Conclusion IL 4 gene modification might enhance the tumor cell specific CTL killing activities by inducing cell surface molecules expression and IL 2 secretion.
出处
《中华血液学杂志》
CAS
CSCD
北大核心
2001年第1期17-19,共3页
Chinese Journal of Hematology
基金
国家自然科学基金!资助项目 (39470 33)
深圳市卫生系统科研课题基金!资助项目 (199940 0 6 )
