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Study For Functional Features of The Dendritic cell

树突状细胞功能特征的研究

基本信息

批准号：
06044124
负责人：
INABA Kayo
金额：
$ 4.16万
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：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

Dendritic cells belong to the myeloid linearge of hematopoietic cells and are the most potent in T cell activation for in the initiation of immune responses. The aim of this project is futher clarification of the functional role of dendritic cells in vivo and in vitro in relation to the cellular development and maturation.1) The NLDC-145 mAb recognizes a 205 kDa integral membrane protein which is expressed at high levels on murine dendritic cells and thymic epithelial cells (DEC-205). We reexamined cell specificity by mean of cytofluorographic and histological approaches and potential function of this molecule. DEC-205 can also be detected on many other subsets of leukocytes, particularly B cells. Although we have been unable to inhibit the alloreactivity that is induced by dendritic cells in vitro and in vivo, DEC-205 is shown to be rapidly internalized via coated pits and vesicles, and delivered to a multivesicular endosomal compartment resembling MIIC.A rabbit anti-DEC-205 IgG is pr … More esented by DCs to rabbit IgG-specific T cell hybridomas 100 times more efficiently than normal rabbit IgG.Considering that DEC-205 is a receptor with 10 C-type lectin domains, this molecule may be a novel endocytic receptor to capture glycoprotein antigens from extracellular space to specialized antigen processing compartment.2) Age-related immunological dysfunction is demonstrated to be ascribable to the decreased T-cell stimulating activity of dendritic cells and B cells in SAMP1 mice. This change is primarily due to the reduced expression of class II and CD54, but not CD80 and CD86.3) The HIV-1 promoter has two key transcriptional controls : NF-kB sites and Sp1 sites. Therefore, we looked for NF-kB and Sp1 factors in different cell types from human and mouse, using many biochemical and electromobility shift assays. Dendritic cells expressed high levels of all known NF-kB,but Sp1 was lacking. Quiescent T cells lacked active NF-kB but expressed Spl.By inducing heterologous dendritic-T cell syncytia, HIV brought together high levels of the essential factors for the viral promoter. This phenomenon would lead to chronic replication of HIV-1 without ostensible immune stimulation. Less

树突状细胞属于造血细胞的髓系，并且在启动免疫应答的T细胞活化中是最有效的。本项目的目的是进一步阐明树突状细胞在体内和体外与细胞发育和成熟相关的功能作用。1）NLDC-145 mAb识别一种205 kDa的整合膜蛋白，该蛋白在小鼠树突状细胞和胸腺上皮细胞（DEC-205）上高水平表达。我们重新检查细胞特异性的细胞荧光和组织学的方法和潜在的功能，这种分子。DEC-205也可以在许多其他白细胞亚群，特别是B细胞上检测到。尽管我们在体内外均不能抑制树突状细胞诱导的同种异体反应性，但DEC-205可通过包被的小凹和囊泡迅速内化，并进入类似于MIIC的多泡内体区室。 ...更多信息 DCs对兔IgG特异性T细胞杂交瘤的表达效率是正常兔IgG的100倍。该分子可能是一种新的内吞受体，将糖蛋白抗原从细胞外空间捕获到专门的抗原加工区。SAMP 1小鼠中树突状细胞和B细胞的细胞刺激活性。这种变化主要是由于II类和CD 54的表达减少，而不是CD 80和CD 86。3）HIV-1启动子有两个关键的转录控制：NF-κ B位点和Sp1位点。因此，我们寻找NF-κ B和Sp1因子在不同的细胞类型从人类和小鼠，使用许多生化和电迁移率变化测定。树突状细胞表达高水平的所有已知的NF-kB，但缺乏Sp1。静止T细胞缺乏活性NF-kB，但表达Spl。通过诱导异源树突状T细胞合胞体，HIV汇集了高水平的病毒启动子必需因子。这种现象将导致HIV-1的慢性复制，而没有表面上的免疫刺激。少