Study on the Specialized Function of Dendritic Cells

树突状细胞特异功能的研究

基本信息

批准号：
08044271
负责人：
INABA Kayo
金额：
$ 4.54万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08044271/
关键词：
dendritic cells antigen-presentation antigen processing MHC class II immune response cell differentiation cell interaction 機能的成熟

项目摘要

Dendritic cells (DC) are distinctive leukocytes that are specialized antigen-presenting cells for T cell mediated immune responses. They acquire antigens in peripheral tissues and migrate to T area of lymphoid organs where they present processed peptides in context of MHC class II to T cells. In normal steady state, 2-3 distinguishable subpopulations of DC in respect of phenotype and function have been reported to locate in lymphoid organs, and it is suggested they may be different not only in maturational steps but also in developmental pathways from precursors. Therefore, we attempted to isolate T area DCs from lymph nodes and characterize phenotype and antigen-presenting and costimulatory functions. We also investigated the features of development and functional maturation of DCs in vivo and in vitro, and antigen-presenting activity after inoculating DNA encoding antigenic determinant recognized by CD4 T cells. The results obtained are 1) T area DCs present high levels of self peptides in addition to MHC class II and various adhesion and costimulatory molecules and induce apoptosis of specific T-T hybridomas, suggesting they regulate self reactivity in the periphery ; 2) Immature early-stage of DCs in which most class II are intracellular and localized to lysosomes, undergo maturation to become highly stimulatory through the intermediate stage, in which intracellular class II are found in peripheral non-lysosomal vesicles. The decrease in rate of class II degradation and increase in expression of surface class II is a fundamental feature of DCs maturation and is also exhibited by a very different population of DC ; 3) DCs isolated either from draining lymph nodes or skin present antigens to T cells and carry plasmid DNA,indicating that the uptake of DNA and/or the protein expressed by DCs triggers immune responses to DNA vaccines.

树突状细胞 (DC) 是独特的白细胞，是 T 细胞介导的免疫反应的专门抗原呈递细胞。它们在外周组织中获取抗原并迁移到淋巴器官的 T 区，在那里它们将 MHC II 类中加工过的肽呈递给 T 细胞。据报道，在正常稳定状态下，在表型和功能方面有2-3个可区分的DC亚群位于淋巴器官中，这表明它们不仅在成熟步骤上而且在与前体的发育途径上可能不同。因此，我们尝试从淋巴结中分离T区DC并表征表型以及抗原呈递和共刺激功能。我们还研究了DC在体内外的发育和功能成熟特征，以及接种编码CD4 T细胞识别的抗原决定簇的DNA后的抗原呈递活性。获得的结果是：1）T区DC除了MHC II类和各种粘附和共刺激分子外，还呈现高水平的自身肽，并诱导特定T-T杂交瘤细胞凋亡，表明它们调节外周的自身反应性； 2) 未成熟的早期 DC，其中大多数 II 类位于细胞内并定位于溶酶体，通过中间阶段成熟变得高度刺激，其中细胞内 II 类存在于外周非溶酶体囊泡中。 II 类降解速率的降低和表面 II 类表达的增加是 DC 成熟的基本特征，并且也由非常不同的 DC 群体表现出来； 3) 从引流淋巴结或皮肤中分离出的 DC 向 T 细胞呈递抗原并携带质粒 DNA，表明 DC 摄取 DNA 和/或表达的蛋白质会触发对 DNA 疫苗的免疫反应。