【摘要】 目的　探讨激发型CD40 单抗 5C11对白血病细胞来源的树突细胞 (DC)的诱导作用及其生物学特性的影响。方法　激发型CD40 单抗 5C11联合不同的细胞因子组合诱导白血病细胞分化为DC ,通过显微镜形态分析 ,流式细胞仪表型分析 ,活细胞计数 ,IL 6、IL 12ELISA定量检测及混合淋巴细胞反应和细胞毒性实验等细胞生物学、免疫学方法对其进行研究。结果　白血病患者外周血或骨髓的白血病细胞 ,在经激发型CD40 单抗 5C11联合不同的细胞因子组合培养后 ,能诱导成为大量成熟的DC ;形态学观察呈现典型的DC特征 ;流式细胞仪检测证实细胞表面上调性表达CD40 、CD80 、CD83 、CD86等分子 ;白血病细胞分化为DC后 ,IL 6分泌量减少 ,IL 12分泌量增加 (P <0 .0 5 ) ;同种异体混合淋巴细胞反应也显示 ,诱导的DC具有很强的刺激同种异体T细胞增殖的能力 ,这种增殖的T细胞对白血病细胞具有一定的杀伤作用。结论　激发型CD40 单抗 5C11联合细胞因子能诱导白血病细胞分化为功能性DC。这可能在白血病的过继免疫疗法中具有潜在的应用价值。更多还原

【Abstract】 Objective To study the impact of an agonist anti-CD_ 40 monoclonal antibody 5C11 on the induction and biological characteristics of leukemic dendritic cells. Methods Combinations of 5C11 and different cytokines were used to induce differentiation of leukemic blasts into dendritic cells. Morphology was observed by light microscopy. Surface antigens of the induced cells were analyzed by fluorescence-activated cell sorting (FACS), the yields of dendritic cell by cell counting, the levels of IL-6 and IL-12 by ELISA, T cell proliferating activity by allo-mixed lymphocyte reaction(MLR) in vitro. Allogeneic T cells were stimulated with leukemic dendritic cells and T-cell cytotoxicity was measured by MTT assay. Results When cultured with combinations of 5C11 and different cytokines, the leukemic cells isolated from the patients could differentiate into dendritic cells. The morphology showed typical features of dendritic cells, which expressed high levels of CD_ 40 ,CD_ 80 and CD_ 86 . In comparison with the ori-ginal leukemia cells, the leukemic dendritic cells secreted less IL-6 but more IL-12( P <0.05). The leukemic dendritic cells were potent to stimulate the proliferation of allogeneic T cells, and the latter was able to lyse the original leukemia cells. Conclusion Leukemic blasts could be induced to differentiate into functional dendritic cells. It may be of great value in the adoptive immunologic therapy of leukemia.更多还原