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α干扰素促进急性髓性白血病来源的树突状细胞的成熟分化
IFN-alpha promotes the full maturation of dendritic cells derived from acute myeloid leukemia cells in vitro
【摘要】 目的:研究α干扰素(interferon alpha,IFN-α)对不同亚型的急性髓性白血病(acute myeloid leukemia,AML)细胞来源的树突状细胞(dendritic cell,DC)免疫表型及功能的影响。方法:5例初发AML患者(其中M2 1例、M4 2例、M5 2例)的外周血单个核细胞,在含GM-CSF、IL-4、TNF-α的无血清培养液中培养11 d,其后加入IFN-α-2a(1 000 U/ml)继续培养3 d,获得DC(IFN-AML-DC),光镜下观察细胞形态,流式细胞仪测定细胞免疫表型,同种异体混和淋巴细胞反应检测DC的免疫功能。结果:所有患者白血病细胞培养14 d后均转化为IFN-AML-DC,与正常人外周血单核细胞由GM-CSF+IL-4+TNF-α培养获得的DC(monocyte-derived DC,MoDC)及AML细胞由GM-CSF+IL-4+TNF-α培养获得的DC(AML-DC)相比,IFN-AML-DC具有典型成熟形态的细胞明显增多,表达CD83+细胞的比例显著增加,HLA-DR、CD86分子的表达水平增高,对同种异体T淋巴细胞的激活能力明显高于MoDC及AML-DC。结论:IFN-α能够促进AML-DC的体外成熟,形成更强的免疫激活能力,为AML的免疫治疗提供更有力的手段。
【Abstract】 Objective: To explore the influences of interferon alpha(IFN-α) on the phenotype and function of dendritic cell(DC) derived from acute myeloid leukemia(AML) cells in vitro.Methods: Peripheral blood mononuclear cells(PBMCs) from 5 AML patients(1 with M2,2 with M4,and 2 with M5) were incubated concurrently with granulocyte-macrophage colony-stimulating factor(GM-CSF),interleukin-4(IL-4),and tumor necrosis factor-α(TNF-α) for 11 days and then IFN-α2(1 000 U/ml) was added for another 3 days′ culture to acquire IFN-AML-DC.The cell morphology was observed under light microscope.Immunophenotypic features and function of IFN-AML-DC were evaluated by flow cytometry and allogeneic mixed lymphocyte reaction(allo-MLR) assay,respectively.Results: DCs were generated from blasts of all patients when cultured with IFN-α/GM-CSF/IL-4/TNFα.Compared with DCs derived from normal PBMCs(GM-CSF+IL-4+TNF-α) and AML cells(GM-CSF+IL-4+TNF-α),more IFN-AML-DCs exhibited morphological and immunophenotypic features of mature DCs,including higher expression level of CD83,HLA-DR,and CD86 and more potent Allo-MLR stimulatory capacity.Conclusion: IFN-α can promote the maturation of AML-DC in vitro, leading to more potent immunoactivating ability,which provides a more effective way for immunotherapy of AML.
【Key words】 interferon alpha; acute myeloid leukemia; dendritic cell; immunotherapy;
- 【文献出处】 中国肿瘤生物治疗杂志 ,Chinese Journal of Cancer Biotherapy , 编辑部邮箱 ,2007年06期
- 【分类号】R733.7
- 【被引频次】3
- 【下载频次】95