本文選題：樹突狀細(xì)胞　切入點(diǎn)：分化　出處：《第一軍醫(yī)大學(xué)》2005年博士論文　論文類型：學(xué)位論文

【摘要】：樹突狀細(xì)胞(dendritic cells,DC)是目前所知的功能最強(qiáng)的、唯一能激活初始(naive)T細(xì)胞的專職抗原呈遞細(xì)胞(antigen presenting cell,APC),在抗原的加工提呈、抗原識(shí)別及T細(xì)胞的激活中發(fā)揮著重要的作用。因此,DC在免疫應(yīng)答及其機(jī)制的研究和腫瘤及病毒感染等的免疫治療中處于極重要地位。在體外,單核細(xì)胞(monocytes,Mo)、CD34~+造血干細(xì)胞(haemopoietic progenitor cells,HPC)及某些髓系白血病細(xì)胞可以被多種細(xì)胞因子誘導(dǎo)而獲得DC的某些免疫表型和功能,并建立了組合性細(xì)胞因子(如GM-CSF、IL-4、TNF-α和SCF等)體外擴(kuò)增培養(yǎng)DC的方法。本課題先對(duì)常規(guī)的組合性細(xì)胞因子誘導(dǎo)DC的表面標(biāo)志與功能進(jìn)行了研究,在此基礎(chǔ)上,探索了鈣離子載體在誘導(dǎo)Mo、HPC及急性白血病細(xì)胞向DC分化中的作用及其信號(hào)機(jī)制。 成熟DC除了具有典型樹突狀細(xì)胞的形態(tài)外,還必須特征性高表達(dá)與抗原提呈有關(guān)的MHC-Ⅰ和MHC-Ⅱ類分子,高水平表達(dá)多種共刺激分子B7—1/CD80、B7-2/CD86及DC的特征性表面標(biāo)志CD83分子,以及明顯刺激T細(xì)胞增殖等功能。在實(shí)驗(yàn)中我們發(fā)現(xiàn),Mo在GM-CSF和IL-4存在條件下4天內(nèi)開始發(fā)生DC的形態(tài)改變,但繼續(xù)培養(yǎng)10天并給予TNF-α刺激后,這些具有典型DC形態(tài)的細(xì)胞其表面共刺激分子的上調(diào)及CD14分子的下調(diào)表達(dá)水平不均一,DC的成熟標(biāo)志CD83分子表達(dá)缺乏。在CD34~+HPC的誘導(dǎo)分化中,第一周給予GM-CSF、TNF-α和SCF培養(yǎng),可將細(xì)胞總數(shù)擴(kuò)增113±29(n=5)倍,第二周給予GM-CSF、IL-4和TNF-α繼續(xù)培養(yǎng),許多有核細(xì)胞獲得DC的形態(tài)及特征性表面標(biāo)志,包括高水平表達(dá)HLA-DR、CD40、CD86和細(xì)胞間黏附分子CD54分子等,但細(xì)胞表面共刺激分子B7-1/CD80及DC的特征性成熟標(biāo)志CD83分子的表達(dá)仍很弱。另外,上述組合性細(xì)胞因子培養(yǎng)獲得的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- 偽 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，

本文編號(hào)：1629375