【摘要】 目的:研究新近发现的免疫调节因子——白细胞介素21(IL-21)对外周血及脐血来源的CIK细胞产生及抗肿瘤活性的体外作用。方法:采集分离正常人的外周血及脐血单个核细胞,加用细胞因子诱导培养CIK细胞,在有无人源IL-21(200ng/μl)培养条件下,检测CIK细胞表达及杀伤K562细胞和急性白血病患者肿瘤细胞活性的变化;检测培养上清IFN-γ的浓度及杀伤活性以及RT-PCR法检测培养细胞的IFN-γRNA表达的不同。结果:在人源IL-21的作用下,培养14天时,CIK细胞的产生由17.5%升至26.5%(外周血来源);33.8%升至55.9%(脐血来源)。②CIK细胞对K562细胞的杀伤作用由24.0%升至52.2%(外周血来源);35.1%升至79.7%(脐血来源);脐血来源CIK细胞对13例急性白血病患者肿瘤细胞杀伤作用由27.4%升至58.3%。③外周血来源培养上清IFN-γ的浓度上升了近一倍,对K562的杀伤作用增加了近一倍;脐血来源培养上清IFN-γ的浓度上升了三倍多,对K562的杀伤作用增加了近二倍;④外周血和脐血来源培养细胞的IFN-γRNA表达均明显增高。结论:人源IL-21可增加外周血及脐血来源CIK细胞产生及增强其抗肿瘤活性,通过增加IFN-γ的表达产生为其作用机制之一,提示IL-21在增强肿瘤免疫治疗中具有潜在的临床应用前景。更多还原

【Abstract】 Objective:To explore the effects of humanized interleukin 21(IL-21)on induction and anti-tumor activity of cytokine inducing killer(CIK)cells derived from both peripheral blood(PB)and cord blood(CB)in vitro.Methods:Mononuclear cells from peripheral and cord blood were separated.The cells were cultured with cytokines to induce CIK cells at the condition.with or without humanized IL-21(200 ng/ml).Quantity of CIK cells and the cytotoxic activity against either K562 cells or leukemia cells from patients were measured.The concentration of the interferon-γ(IFN-γ)in the culture supernatant was measured by enzyme immunoassay;The quantity of IFN-γ RNA was measured by RT-PCR assay,and the cytotoxic activity against K562 cells by culture supernatant was also measured.Results:Cultured with IL-21,at day 14,the quantity of CIK cells was increased from 17.5% to 26.5%(PB original)and from 33.8% to 55.9%(CB original).Cytotoxic activity against K562 cells by CIK cells was increased from 24.0% to 52.2%(PB original)and from 35.1% to 79.7%(CB original);The cytotoxic activity against leukemia cells from 13 patients by CIK cells derived from CB was increased from 27.4% to 58.3%.The concentration of IFN-γ in the culture supernatant was increased for almost one fold(PB original),and for more than 3 folds(CB original);The cytotoxic activity against K562 cells by the culture supernatant was increased for almost one fold(PB original)and for almost two folds(CB original).The expression of IFN-γ RNA in CIK cells was obviously increased in both PB and CB original cells.Conclusion:Humanized IL-21 could enhance the production of CIK cells and their anti-tumor activity in vitro.The increased expression of interferon-γ mediate the effects in IL-21 stimulation.These data indicate that IL-21 has a potential clinic value in the enhancement of anti-tumor immunotherapy.更多还原