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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 designed to investigate the in vitro effect of interleukin-21 (IL-21) on dendritic cells (DCs) -induced CTL anti-leukemia in vitro. DCs were induced by different cytokines in acute leukemia (AL) patients and the autologous T lymphocytes were induced to co-culture with autologous T lymphocytes to induce leukemia-specific DCs. LDH release assay CTL killed autologous AL cells, and detect the changes of IFN-γ and TNF-α produced by CTL. The experiment was divided into two groups: experimental group, IL-21 (200ng / ml) was added during DC-CTL co-culture; control group without IL-21. At the same time, the cultured DCs were treated with IL-21 alone to detect the changes of surface antigen expression and the ability to induce allo-mixed lymphocyte reaction. The results showed that the rates of CTL production in control group and experimental group were (56.73 ± 10.21)% and (73.43 ± 18.01)%, respectively (p <0.01). The levels of IFN-γ and TNF- ± 67.20 ng / L, 310.62 ± 141.15 ng / L (p <0.01) and (8.77 ± 5.09) μg / L and (15.25 ± 6.56) μg / L respectively. When the target ratio was 20:1, the cytotoxicity of the two groups on autologous AL cells were (50.22 ± 5.07)% and (75.38 ± 9.47)%, respectively (p <0.01) , There was no significant change in the expression of CD83, CD86, CD80 and HLA-DR. There was no significant difference in the ability to induce allogeneic mixed lymphocyte reaction. IL-21 could promote the proliferation of CTL induced by DC, increase the production of IFN-γ and TNF-α and enhance its anti-leukemia effect; IL-21 had no significant effect on the expression of mature DC surface antigen and its immune function; In leukemia immunotherapy play a role, with potential clinical value.