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

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。

Objective： To explore the influences of interferon alpha （IFN-α） on the phenotype and function of dendri tic 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 MS） were incubated concurrently with granulocytemacrophage colony-stimulating factor （ GM-CSF）, interleukin4 （ IL4 ）, and tumor necrosis factor-α （TNF-α） for 11 days and then IFN-α 2 （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/IL4/TNF-α. Compared with DCs derived from normal PBMCs （ GM-CSF ＋ IL4 ＋ TNF-α） and AML cells （ GM-CSF ＋ IL4 ＋ 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.