CD40信号对小鼠树突状细胞极化Th细胞和上调B7-H3分子表达的作用及其生物学意义
发布时间：2019-06-05 05:04
【摘要】：树突状细胞(Dendritic cells,DCs)是目前已知的体内最重要的专职性APC,能摄取、加工及提呈抗原,刺激初始型T细胞的活化和增殖,是启动、调控并维持特异性免疫应答的中心环节。DCs介导的T细胞免疫应答在机体抗肿瘤免疫中发挥主导作用,包括对抗原特异性T细胞的诱导、激发、扩增和功能介导等。业已表明,DCs和Th细胞的极化诱导密切相关,不同的抗原致敏和致DCs成熟信号可能会赋予DCs不同的介导T细胞极化能力。凋亡肿瘤细胞可以提供DCs丰富的肿瘤抗原,能够提供多个MHC-Ⅰ和MHC-Ⅱ两类途径的抗原表位,因而采用凋亡肿瘤细胞作为抗原可以有效获得肿瘤特异性树突状细胞。CD40/CD40L信号被认为是DCs发育成熟至关重要的信号,CD4~+T细胞与DCs表面CD40L-CD40的相互作用对T细胞和DCs的功能均产生重要影响。利用CD40信号激发在体外可望获得表型和功能上成熟的树突状细胞。 本研究第一部分利用共聚焦显微镜观察了未成熟树突状细胞对凋亡肿瘤细胞的摄取,采用流式细胞术和~3H-TdR掺入实验研究了CD40和TNFR信号对凋亡肿瘤细胞负载的树突状细胞表型的促成熟作用和促T细胞增殖效应,采用胞内染色、流式细胞术和ELISA探讨了CD40配基化的肿瘤特异性树突状细胞对Th细胞的极化作用,发现CD40较TNFR信号更能增强树突状细胞介导Th细胞向Th1细胞极化的能力。 论文第二部分试图从共刺激分子的激发和调节性表达角度探讨DCs对Th细胞极化的作用。首先采用RT-PCR和流式细胞术分析了CD40信号对树突状细胞表面B7-H3分子表达的调节作用,发现了CD40信号能上调树突状细胞上B7-H3分子的表达,并进一步采用特异性抗B7-H3抗体阻断实验、~3H-TdR掺入实验和ELISA发现了B7-H3分子的上调性表达有利于树突状细胞介导Th1型免疫应答。同时还发现CD40信号促进凋亡肿瘤细胞负载的树突状细胞IFN-γ的分泌,推测CD40信号上调树突状细胞上B7-H3分子的表达可能和其介导IFN-γ
[Abstract]:Dendritic cells (Dendritic cells,DCs) are the most important specialized APC, known to ingest, process and present antigens, stimulate the activation and proliferation of initial T cells. The central link of regulating and maintaining specific immune response. DCS mediated T cell immune response plays a leading role in antitumor immunity, including induction, stimulation, amplification and function mediated by antigenic specific T cells. It has been shown that the polarization induction of DCs and Th cells is closely related, and different antigen sensitized and DCs mature signals may endows DCs with different polarization ability of T cells. Apoptotic tumor cells can provide DCs rich tumor antigens and provide multiple epitopes of MHC- 鈪，
本文编号：2493275
[Abstract]:Dendritic cells (Dendritic cells,DCs) are the most important specialized APC, known to ingest, process and present antigens, stimulate the activation and proliferation of initial T cells. The central link of regulating and maintaining specific immune response. DCS mediated T cell immune response plays a leading role in antitumor immunity, including induction, stimulation, amplification and function mediated by antigenic specific T cells. It has been shown that the polarization induction of DCs and Th cells is closely related, and different antigen sensitized and DCs mature signals may endows DCs with different polarization ability of T cells. Apoptotic tumor cells can provide DCs rich tumor antigens and provide multiple epitopes of MHC- 鈪，
本文编号：2493275
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