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IL-12与IL-18在体外培养系统中诱导肿瘤特异性CTL杀伤活性的比较

方艳秋1,齐亚灵1,严莉2,谭岩1,段秀   

  1. (1.吉林大学第一医院中心实验室 吉林省卫生厅生物治疗及基因诊断重点实验室,吉林 长春130021;2. 吉林省长春市中心血站,吉林 长春 130051;3.东北师范大学生命科学学院,  吉林 长春130024)
  • 收稿日期:2007-06-28 修回日期:1900-01-01 出版日期:2007-11-28 发布日期:2007-11-28
  • 通讯作者: 谭岩

Comparison of cytotoxicity of tumor specific CTL inducedby IL-18 and IL-12 in cell co-culture system in vitro

FANG Yan-qiu1,QI Ya-ling1,YAN Li2,TAN Yan1,DUAN Xiu-mei1,XU Shu-fen1,LIU Jin-sha3   

  • Received:2007-06-28 Revised:1900-01-01 Online:2007-11-28 Published:2007-11-28
  • Contact: TAN Yan

摘要: 目的:分别应用重组人白细胞介素12(rhIL-12)及重组人白细胞介素18(rhIL-18)在体外培养系统(CCs)中诱导肿瘤特异性细胞毒性T淋巴细胞(CTL),比较IL-18与IL-12诱导的肿瘤特异性CTL的杀伤活性,探索IL-18的抗肿瘤作用机制。方法:采用Stem SepTM免疫磁性细胞分离法分离人外周血NK细胞、T细胞及DCs细胞,流式细胞仪分析细胞表型,125I-UdR标记的细胞毒实验检测杀伤活性。结果:在CCs中、在肿瘤抗原存在的条件下,rhIL-18和rhIL-12均能诱导产生针对U251、MCF7特异性CTL,其作用能力与rhIL-18和rhIL-12的浓度呈剂量依赖关系,但rhIL-18诱导肿瘤特异性CTL的作用明显高于rhIL-12(P<0.01);rhIL-18和rhIL-12在诱导肿瘤特异性CTL过程中具有协同作用,两者联合应用诱导肿瘤特异性CTL的能力明显高于单独应用rhIL-18和rhIL-12(P<0.01)。结论:rhIL-18和rhIL-12在CCs中均能够诱导并促进CTL介导的肿瘤特异性杀伤效应,rhIL-18诱导的肿瘤特异性CTL的能力明显高于rhIL-12,两者在诱导肿瘤特异性CTL过程中具有协同作用。

关键词: 白细胞介素18, 白细胞介素12, T淋巴细胞, 细胞毒性

Abstract: To compare the efficiency of IL-18 and IL-12 in inducing the tumor specific CTL in vitro,and test the cytotoxicities of tumor specific CTL induced in the same culture system with IL-18 or IL-12. MethodsThe NK cells,T cells and dendritic cells were separated from fresh PBMNCs by using the Stem SepTM immunomagnetic beads.Cell phenotypes of the purified cell populations were identified with FCM technique.The cell co-culture system was established as follows:the cell preparations in which definite cell subset had been deleted was co-cultivated with mitotic-inactivated tumor cells in the presence of rhIL-18 and/or rhIL-12.Cytotoxicities of the various effector cell preparations to a series of tumor cell lines were examined by the isotope releasing assay.Results In the  cell co-culture system in vitro,rhIL-18 or rhIL-12 alone and dose-dependently induced tumor specific cytotoxicities.The level of cytolytic activity of the tumor specific CTL induced by IL-12 was substantially inferior to that induced by IL-18 (P<0.01). ConclusionThese results suggest that IL-12 does not induce tumor-specific CTL as efficiently as IL-18 does in this co-culture system under these conditions,but the synergistic effect could be observed during administration of IL-18 and rIL-12.

Key words: interleukin-18, interleukin-12, T-lymphocytes, cytotoxic

中图分类号: 

  • R392.11