CD40分子在树突状细胞抗人多发性骨髓瘤免疫应答中的作用及其机理

目的为研究CD40分子在人树突状细胞(DC)抗多发性骨髓瘤(MM)中的作用及其机制。方法采用CD40配体(CD40L)转基因细胞及抗CD40的激发型单克隆抗体在体外激发DC，并通过DC细胞计数、形态学和细胞表型分析、IL-12定量检测、DC对MM抗原的摄取及混合淋巴细胞反应等手段对其进行研究。结果CD40分子配基化可促进DC的体外增殖和分化，使DC增加分泌IL-12,并下调DC摄取抗原的能力，促进DC的成熟，同时赋予DC激发自体CD8+细胞增殖的作用，使后者对MM细胞产生特异性的杀伤作用。结论CD40分子激发不仅有利于DC的增殖、分化和增强激发T细胞增殖，而且Th细胞表达的CD40L是DC获得直接激发抗MM抗原特异性CD8+T细胞的关键分子。

The role of CD40 on dendritic cells in the anti-multiple myeloma immune response

Objective:To study the function of CD40 of dendritic cells (DC) in the anti multiple myeloma immune response. Methods:CD40 ligand (CD40L) transgenic cos cells and anti CD40 agonist monoclonal antibody were used to stimulate the CD40 of DC. The proliferation, morphology, and phenotype of DC were observed. Furthermore, the ability to express IL 12 and to stimulate the proliferation of T cells in autologous MLR were also examined. Results: The proliferation of DC and the costimulatory molecule were up regulated by activating CD40. After CD40 activation, DC showed enhanced IL 12 expression, and reduced less Ig FITC uptake in the experiment. Moreover, anti MM specific CD8 T cells could be induced by DC, exposed to MM antigen, in the presence of CD4 T cells. The function of CD4 T cells could be replaced by CD40L. Conclusion: The results show that the activation of CD40 not only promotes the proliferation and differentiation of DC, but is also the signal from CD4 Th cells necessary for the activation of DC.