Wang Zheng-fei, Yu Ge-hua, Zhu Zi-ling, Zhu Yi-pei, Wang Feng-ming, Pan Jian-zhong, Gu Zong-jiang, Zhang Xue-guang
Biotechnology Institute of Suzhou University, Suzhou 215007, China.
Zhonghua Xue Ye Xue Za Zhi. 2003 Nov;24(11):572-5.
To study the impact of an agonist anti-CD(40) monoclonal antibody 5C11 on the induction and biological characteristics of leukemic dendritic cells.
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.
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 original 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.
Leukemic blasts could be induced to differentiate into functional dendritic cells. It may be of great value in the adoptive immunologic therapy of leukemia.
研究激动型抗CD40单克隆抗体5C11对白血病树突状细胞诱导及生物学特性的影响。
采用5C11与不同细胞因子联合诱导白血病原始细胞分化为树突状细胞。通过光学显微镜观察形态。用荧光激活细胞分选术(FACS)分析诱导细胞的表面抗原,通过细胞计数检测树突状细胞产量,用酶联免疫吸附测定法(ELISA)检测白细胞介素-6(IL-6)和白细胞介素-12(IL-12)水平,体外通过同种异体混合淋巴细胞反应(MLR)检测T细胞增殖活性。用白血病树突状细胞刺激同种异体T细胞,并用MTT法测定T细胞细胞毒性。
与5C11和不同细胞因子联合培养时,从患者分离的白血病细胞可分化为树突状细胞。形态显示出树突状细胞的典型特征,其高表达CD40、CD80和CD86。与原始白血病细胞相比,白血病树突状细胞分泌的IL-6较少,但IL-12较多(P<0.05)。白血病树突状细胞能有效刺激同种异体T细胞增殖,后者能够裂解原始白血病细胞。
白血病原始细胞可被诱导分化为功能性树突状细胞。这在白血病的过继免疫治疗中可能具有重要价值。