Cao X, Zhao Y, Yu Y, Wang Y, Zhang M, Zhang W, Wang J
Department of Immunology, Second Military Medical University, 800 Xiang Yin Road, Shanghai 20 0433, China.
Immunology. 1998 Sep;95(1):141-7. doi: 10.1046/j.1365-2567.1998.00566.x.
Dendritic cells (DC) are professional antigen-presenting cells (APC) within the immune system and antigen-pulsed DC can be used as an effective vaccine for active immunotherapy of cancer. Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in the generation of DC. We previously showed that GM-CSF can induce murine erythroleukaemia cells (FBL-3) to differentiate into monocyte-like cells. To develop a new vaccinating method to stimulate the host immune response to leukaemia, we further investigate whether FBL-3 cells induced by GM-CSF can differentiate into DC in the present study. After being treated with GM-CSF, FBL-3 cells expressed high levels of 33D1 and NLDC-145, which are the specific markers of DC. The expression of MHC-II, B7-1, B7-2 and vascular cell adhesion molecule-1 (VCAM-1) was up-regulated markedly; the typical morphology of DC were also observed by electron microscopy. Functionally, the GM-CSF-induced FBL-3 cells could apparently stimulate the proliferation of naive allogeneic and autologous T lymphocytes and induce the generation of specific CTL more efficiently than the wild-type FBL-3 cells. Mice immunized with GM-CSF-induced FBL-3 cells could resist the subsequent challenge with the wild-type FBL-3 cells. Collectively, these data indicate that GM-CSF differentiates murine erythroleukaemia cells into DC phenotypically, morphologically and functionally. FBL-3-derived DC can be used as a new type of vaccine. Our results may have important implications for the immunotherapy of leukaemia.
树突状细胞(DC)是免疫系统中的专职抗原呈递细胞(APC),抗原脉冲DC可作为癌症主动免疫治疗的有效疫苗。粒细胞-巨噬细胞集落刺激因子(GM-CSF)在DC的生成中起重要作用。我们之前表明GM-CSF可诱导鼠红白血病细胞(FBL-3)分化为单核细胞样细胞。为开发一种新的疫苗接种方法以刺激宿主对白血病的免疫反应,我们在本研究中进一步探究GM-CSF诱导的FBL-3细胞是否能分化为DC。用GM-CSF处理后,FBL-3细胞高水平表达DC的特异性标志物33D1和NLDC-145。MHC-II、B7-1、B7-2和血管细胞黏附分子-1(VCAM-1)的表达也明显上调;通过电子显微镜也观察到了DC的典型形态。在功能上,GM-CSF诱导的FBL-3细胞比野生型FBL-3细胞能更明显地刺激幼稚同种异体和自体T淋巴细胞的增殖,并更有效地诱导特异性CTL的产生。用GM-CSF诱导的FBL-3细胞免疫的小鼠能够抵抗随后野生型FBL-3细胞的攻击。总体而言,这些数据表明GM-CSF在表型、形态和功能上将鼠红白血病细胞分化为DC。FBL-3来源的DC可作为一种新型疫苗。我们的结果可能对白血病的免疫治疗具有重要意义。