人源白细胞介素21对外周血及脐血来源CIK细胞产生和抗肿瘤活性的作用研究  

Effects of humanized interleukin 21 on the production and anti-tumor activity of cytokine induced killer cells derived from both peripheral and cord blood

作　　者：赵明峰[1] 邓琦[1] 李玉明[1] 林雪梅[1] 刘鹏江[1] 耿丽[1] 李敬兰[1] 

机构地区：[1]天津市第一中心医院血液肿瘤科,天津300192

出　　处：《中国免疫学杂志》2008年第9期794-799,共6页Chinese Journal of Immunology

基　　金：天津市卫生局科技基金(05KY10);教育部留学归国人员科研启动基金(教外司留[2007]1108号)

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。Objective： To explore the effects of humanized interleukin 21 （ 1L-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 ceils 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 intefferon-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. Condusiom Humanized IL21 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.

关 键 词：人源自细胞介素21 CIK细胞 肿瘤免疫治疗 外周血 脐血 

分 类 号：R3[医药卫生—基础医学]