白介素21对树突状细胞诱导的CTL抗白血病作用的影响  

Effects of Interleukin 21 on Anti-leukemia Activity of Cytotoxic T Lymphocytes Induced by Dendritic Cells

作　　者：赵明峰[1] 翟文静 邓琦[1] 李玉明[1] 耿丽[1] 杨莉[1] 吕海容[1] 林雪梅[1] 刘鹏江[1] 李敬兰[1] 

机构地区：[1]天津市第一中心医院血液科,天津300192 [2]中国医学科学院、北京协和医学院血液学研究所、血液病医院,天津300020

出　　处：《中国实验血液学杂志》2009年第3期627-632,共6页Journal of Experimental Hematology

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

摘　　要：本研究探讨白介素21(IL-21)对树突状细胞(DC)诱导的CTL抗白血病的体外作用。以不同细胞因子诱导培养急性白血病(AL)患者缓解期外周血单个核细胞产生DC,自体AL细胞RNA作为抗原负载DC,与自体T淋巴细胞共培养诱导白血病特异性CTL产生;用LDH释放法检测CTL杀伤自体AL细胞的作用,并检测CTL产生IFN-γ和TNF-α的变化。实验共分2组:实验组,在DC-CTL共培养过程中加用IL-21(200ng/ml);对照组,不加IL-21。同时对IL-21单独作用培养后成熟DC,检测其表面抗原表达变化以及诱导同种混合淋巴细胞反应能力。结果表明:对照组和实验组的CTL产生率分别为:(56.73±10.21)%,(73.43±18.01)%(p<0.01);培养上清中IFN-γ和TNF-α分别为:(154.91±67.20)ng/L,(310.62±141.15)ng/L(p<0.01)和(8.77±5.09)μg/L,(15.25±6.56)μg/L(p<0.01)。在效靶比为20∶1时,两组对自体AL细胞的杀伤作用分别为(50.22±5.07)%,(75.38±9.47)%(p<0.01);IL-21作用后的成熟DC的CD1a、CD83、CD86、CD80和HLA-DR表达没有明显变化;诱导同种混合淋巴细胞反应能力亦没有明显不同。结论:IL-21可促进DC诱导的CTL增殖、增加IFN-γ和TNF-α产生从而增强其抗白血病作用;IL-21对成熟DC表面抗原表达及其免疫功能无明显影响;提示IL-21在白血病免疫治疗中发挥一定的作用,具有潜在的临床应用价值。This study was aimed to explore the effects of interleukin 21 （ IL-21 ） on the anti-leukemia activity of cytotoxic T lymphocytes （CTL） induced by dendritic cells （DCs） in vitro. The peripheral mononuclear cells from leukemia patients in complete remission were cultured with the specific cytokines to induce the production of DCs. The DCs loaded with RNA from autologous leukemic cells as antigen, and co-cultured with autologous T lymphocytes to get leukemia speaific CTL. The cytotoxic activity of CTL against autologous leukemic ceils was measured by LDH release method. The concentration of IFN-γand TNF-α in the culture supematant was measured by enzyme immunoassay. The effects of IL-21 on the mature DCs were also studied by the measurement of the phenotype of DC and the allogenic mixed lymphocytic reactions induced by DCs. Experiments were divided into 2 groups： test group in which IL-21 （200 ng/ml） was added in coculture of DC/CTL and control group in which no IL-21 （200 ng/ml） was added. The results showed that when cultured with IL-21, the quantity of CTL increased from （56.73 ± 10.21 ）% （control group） to （73.43 ± 18.01 ） % （p 〈0.01 ） ; The concentration of IFN-γ and TNF-α in the culture supematant increased from（ 154. 91 ± 67.20 ） ng/L （ control group ） to （ 310.62 ± 141.15 ） ng/L （ p 〈 0.01 ） and from （ 8.77 ± 5.09 ） μg/L （ control group ） to （15.25 ±6.56）μg/L（p 〈0.01 ） respectively. At the effector ：target ratio of 20： 1, the cytotoxic activity against autologous leukemic cells by CTL increased from （ 50.22± 5.07 ） % （ control group） to （ 75.38 ± 9.47 ） % （p 〈 0.01 ）. IL-21 had neither effect on the phenotype （CD1 a, CD83, CD86, CD80 and HLA-DR） of mature DCs nor the allogeneic mixed lymphocytic reactions induced by DCs. It is concluded that IL-21 can strengthen the proliferation of CTL, and improve the production of IFN-γand TNF-α, thus enhance the anti-leukemia activity of CTL. Nevertheless

关 键 词：白介素21 树突状细胞 CTL细胞 抗白血病作用 

分 类 号：R733.7[医药卫生—肿瘤] R979.1[医药卫生—临床医学]