【作者】 张烽；

【导师】 顾宗江； 张学光；

【作者基本信息】 苏州大学 ， 免疫学， 2006， 硕士

【摘要】 树突状细胞(DCs)是目前所知体内功能最强的抗原提呈细胞(APCs)，其特点是能够显著刺激初始T细胞增殖。作为机体免疫应答的始动者，DCs在免疫应答的诱导中具有独特的地位。未成熟DCs能摄取抗原并将其处理成免疫原性多肽，以MHC分子-抗原肽复合物的形式表达于细胞表面，供抗原特异性T细胞受体(TCR)识别。在这过程中未成熟DCs逐渐发育成熟。成熟DCs与T细胞之间通过共刺激分子受体与配体间的相互作用激活抗原特异性T细胞，启动免疫应答。 DCs在摄取抗原或接受到某些刺激因素(主要是炎性信号如LPS、IL-1、TNF-α)后，可以分化成熟，其MHC分子、共刺激分子、粘附分子的表达显著提高，激发T细胞的能力得到增强，但其抗原摄取加工能力大大降低。 4-1BB与其配体4-1BBL是一对重要的共刺激分子，对于活化T细胞，参与T细胞介导的免疫应答具有重要意义。4-1BB为TNFR超家族成员，表达于T细胞、NK细胞、NKT细胞和DCs等细胞表面，4-1BBL表达在B细胞、T细胞、巨噬细胞和DCs等细胞上。4-1BB和4-1BBL在DCs上的共表达及它们对于DCs功能的影响正日益受到人们的关注。 本研究第一部分采用小鼠髓系树突状细胞(BMDCs)开展研究。首先证实了BMDCs表面共表达功能性4-1BB及4-1BBL，进而研究了TNF-α、LPS、IFN-γ、CD40配体(CD40L)等成熟活化因子刺激48h后，BMDCs上4-1BB和4-1BBL的表达变化。结果表明，各成熟活化因子均能显著上调BMDCs上4-1BB和4-1BBL的表达，并能有效拮抗负性调控因子IL-10下调DCs上4-1BB和4-1BBL表达的作用。 第二部分研究了激发型4-1BB单克隆抗体2A对BMDCs及小鼠DC细胞系(DC2.4)成熟活化的影响。结果显示，2A刺激BMDCs 48h后，细胞表现出成熟DCs的表型和功能特征，即共刺激分子CD40、CD80、CD86上调表达；摄取Dextran能力更多还原

【Abstract】 Dendritic cells (DCs) are the most powerful antigen presenting cells in vivo with notable characteristics of significantly stimulating the naive T cell proliferation. As a initiator of adaptive immunity, DCs play an important role in inducing the immune responses. Immature DCs uptake, process antigens and present antigen peptides to MHC. Only in this way, can Ags be recognized by TCR on T cells. Accomanied with the interactions between the receptors and ligands of costimulatory molecules on DCs and T cells, the antigen-specific T cells were activated and the immune responses generate.Not only the surface molecules on DCs but the functions change in the maturation process of DCs. In brief, the abilities of capturing and processing antigens, migration degress while the abilities of Ags presentation, T cell activation and cytokine secretion obviously enhance. DCs can be stimulated to mature by pathogen productions, cytokines and costimulatory molecules derived from T cells.4-1BB and its ligand 4-1BBL is a pair of important costimulatory molecules in the activation of T cells and the priming of the immune responses induced by T cells. 4-1BB which was expressed on T cells, natural killer cells, NKT cells and DCs is a member of TNFR superfamily while 4-1 BBL was expressed on B cells, T cells, macrophages and DCs. The coexpression of 4-1BB and 4-1 BBL on DCs and the underlying significance on DCs are highlighted.In the first part of this study, the coexpression of 4-1BB and 4-lBBL on the murine bone marrow-derived dendritic cells (BMDCs) was confirmed and sequently the expression regulation of the costimulatory molecules 4-1BB and 4-lBBL on DCs by DC maturation and activation factors such as TNF-α LPS IFN-γ and CD40L was investigated. The results showed that expressions of 4-1BB and 4-1 BBL were obviously up-regulated更多还原