IFN-γ对体外培养系统中IL-18诱导的肿瘤快速杀伤效应的影响

Effect of IFN-γ on the Rapid Cytotoxicity against Tumor Cells Induced by rhIL-18 in the Cell Co-culture System

目的 :建立体外培养系统 ( CCs) ,应用 rh IL- 1 8在 CCs中诱导肿瘤快速杀伤效应 ,探讨IFN- γ在快速杀伤效应中的作用。方法 :采用 Stem Sep TM免疫磁性细胞分离法分离人外周血 NK细胞、T细胞及树突状细胞 ( DCs) ;流式细胞仪分析细胞表型 ;细胞毒实验检测杀伤活性 ;ELISA方法检测 IFN-γ的产生量。结果 :在 CCs中 ,rh IL- 1 8能单独诱导一种快速肿瘤杀伤作用 ,其杀伤作用随rh IL- 1 8浓度的增加而增高 ;rh IL- 1 8能够诱导 CCs产生 IFN-γ,并促进 m RNA的表达 ,但其作用不如 rh IL- 1 2 + rh IL- 1 8明显 ;抗 IFN- γ单抗对 rh IL- 1 8诱导的快速肿瘤杀伤效应无明显影响。结论 :IL- 1 8能够在 CCs中有效地诱导快速肿瘤杀伤效应 ,且这种杀伤效应不依赖 IFN-

Objective: To investigate the effects of inducible IFN γ on the early activation of NK cytotoxicity in the cell co culture system (CCs) in vitro elicited by rhIL 18. Methods: The NK cells, T cells and dendritic cells were separated from fresh PBMNCs by using the Stem Sep TM immunomagnetic beads. Cell phenotypes of the purified cell populations were identified with FCM technique. Production of IFN γ was measured by ELISA. Cytotoxicities of the various effector cell preparations to a series of tumor cell lines were examined by the isotope releasing assay. Results: In the CCs in vitro , rhIL 18 alone rapidly and dose dependently induced activation of the cytolytic responses against various tumor cell lines mediated by PBMNCs or the separated effector cell populations. Addition of rhIL 18 alone also stimulated the expression and secretion of IFN γ though the stimulation was obviously enhanced by the presence of suboptimal dose of IL 12. It was surprisingly noticed that moAb specific to IFN γ did not interfere with the induced cytotoxic responses. Conclusion: IL 18 could effectively induce a rapid activation of NK cytotoxicity against tumor cells, which may not depend on the modulation of inducible IFN γ production.