钙离子载体在树突状细胞诱导分化中的作用及其信号机制

发布时间：2018-03-18 11:19

  本文选题：树突状细胞　切入点：分化　出处：《第一军医大学》2005年博士论文　论文类型：学位论文

【摘要】：树突状细胞(dendritic cells,DC)是目前所知的功能最强的、唯一能激活初始(naive)T细胞的专职抗原呈递细胞(antigen presenting cell,APC),在抗原的加工提呈、抗原识别及T细胞的激活中发挥着重要的作用。因此,DC在免疫应答及其机制的研究和肿瘤及病毒感染等的免疫治疗中处于极重要地位。在体外,单核细胞(monocytes,Mo)、CD34~+造血干细胞(haemopoietic progenitor cells,HPC)及某些髓系白血病细胞可以被多种细胞因子诱导而获得DC的某些免疫表型和功能,并建立了组合性细胞因子(如GM-CSF、IL-4、TNF-α和SCF等)体外扩增培养DC的方法。本课题先对常规的组合性细胞因子诱导DC的表面标志与功能进行了研究,在此基础上,探索了钙离子载体在诱导Mo、HPC及急性白血病细胞向DC分化中的作用及其信号机制。 成熟DC除了具有典型树突状细胞的形态外,还必须特征性高表达与抗原提呈有关的MHC-Ⅰ和MHC-Ⅱ类分子,高水平表达多种共刺激分子B7—1/CD80、B7-2/CD86及DC的特征性表面标志CD83分子,以及明显刺激T细胞增殖等功能。在实验中我们发现,Mo在GM-CSF和IL-4存在条件下4天内开始发生DC的形态改变,但继续培养10天并给予TNF-α刺激后,这些具有典型DC形态的细胞其表面共刺激分子的上调及CD14分子的下调表达水平不均一,DC的成熟标志CD83分子表达缺乏。在CD34~+HPC的诱导分化中,第一周给予GM-CSF、TNF-α和SCF培养,可将细胞总数扩增113±29(n=5)倍,第二周给予GM-CSF、IL-4和TNF-α继续培养,许多有核细胞获得DC的形态及特征性表面标志,包括高水平表达HLA-DR、CD40、CD86和细胞间黏附分子CD54分子等,但细胞表面共刺激分子B7-1/CD80及DC的特征性成熟标志CD83分子的表达仍很弱。另外,上述组合性细胞因子培养获得的DC除了表面共刺激分子、黏附分子及某
[Abstract]:Dendritic cells (DC) is the most powerful antigen presenting cell, the only professional antigen presenting cell that can activate the initial naive T cell, antigen presenting cell, is presented in the processing of antigen. Antigen recognition and T cell activation play an important role in the study of immune response and its mechanism, as well as in the immunotherapy of tumor and virus infection. Monocytes and some myeloid leukemia cells can be induced by various cytokines to obtain some immunophenotypes and functions of DCs. A method was established to amplify and culture DC by combinatorial cytokines (such as GM-CSFT-IL-4TNF- 伪 and SCF, etc.). The surface markers and functions of DC induced by conventional cytokines were studied in this paper. The role of calcium carrier in inducing the differentiation of HPC and acute leukemia cells into DC and its signal mechanism were investigated. In addition to the typical dendritic cell morphology, mature DC must express the MHC- 鈪，

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