Myeloid dendritic cells and lymphoid dendritic cells

骨髓树突状细胞和淋巴树突状细胞

基本信息

批准号：
11470085
负责人：
INABA Kayo
金额：
$ 9.22万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

项目摘要

Dendiritic cells (DCs) consist of heterogeneous populations in terms of phenotype and function. Such heterogeneity is ascribed to the difference not only in maturation stage but also in origin of precursor cells. In this study, we conducted experiments to clarify differentiation and maturation of dendritic cell in relation to their functions as a potent antigen presenting cells and obtained the following results.1) When fluorescenated microspheres were injected, monocytic cells induced into the injection site engulfed microspheres. Most of them became macrophages, but about 25% of them migrated into the draining ymph nodes and showed immature dendritic cells phenotype. Microsphere-transporting cells were distinct from resident skin DCs, and this transport was reduced by more than 85% in monocyte-deficient op/op mice.2) CD11c^+ CD1^+ cells in lineage- population of human peripheral blood mononuclear cells was found to be the direct precursors of epidermal Langerhans cells, because of th … More e rapid expression of E-cadherin, Langerin and Birbeck granules in the presence of TGF-β1 relative to monocyte-derived dendritic cells.3) Type I IFN (IFN-α/β) produced from CD11c^- plasmacytoid dendritic cells was a potent inhibitor for he spontaneous maturation of plasmacytoid dendritic cells. Although IFN-α/β as well as IFN-γ induced the upregulation of MHC class II and various costimulatory molecules on CD11c^+ DCs, IFN-α/β did not induce IL-12 production and rather promote IL-10 production. In addition, IFN-α/β blocked the effect of IFN-γ and rendered dendritic cells to skew T cell activation towards Th0 and/or Th2.4) Antigen presentation in concert with MHC class II was strictly dependent on maturation stimuli. Endocytosed protein antigen was delivered info late endosome/lysosome compartment (MIIC), but MHC-peptide complex did not form unless the DCs are exposed to inflammatory mediators. Once stimulated, however, and MHC-peptide complexes are transported onto cell surface via CIIV with MHC class I and costimulatory molecules, and the MHC and costimulatory molecules remained clustered. The increased ability of maturing DCs to load MHC class II molecules with antigenic cargo contributed to the >100-fold enhancement of the subsequent primary immune response observed when immature and mature DCs are compared as immune adjuvants in culture and in mice.5) Epidermal Langerhans cells, which is one of the most long-lived dendritic cells in situ, was found to keep migrating to the draining lymph node by phagocytosing keratin-particles in epidermis and dermis using mgf- or hgf-transgenic mice.6) In steady state, T area dendritic cells that were continuously migrated from peripheral tissues were shown to induce immunological tolerance of antigen-specific T cells by targeting antigen using DEC-205 antibody. Tolerance induction was due to the deletion of specific T cells after transient proliferation by IL-2 without IFN-γ production. This step was blocked by the concomitant administration of anti-CD40 mAb to stimulate dendritic cells with antigen. Less

在本研究中，在表型和功能方面的非均质细胞（DC）在YN成熟阶段。并获得了以下结果。1）单核细胞诱导了注射部位的英式微粒，并显示出未成熟的树突状细胞表型。在人周围血液单核细胞的谱系群中，CD11C^+ CD1^+细胞的cd11c^ - 质量骨囊性树突状细胞产生的E-钙粘着蛋白衍生的树突状细胞的PID表达是一种有效的抑制剂。浆细胞性树突状细胞的评分。此外，IFN-α/β仍在严格地与MHC II的抗原呈现抗原表现，使IFN-γ的效果严格呈现在成熟的蛋白质上。内体/裂解体室（MIIC）MHC肽复合物使DC通过MHC I类和Costimimimulation Molecules和MHC MHC和MHE MHC和Costimimulatory Molecules的ciiv进行了炎症介体。在用抗原货物的负载分子中，当未成熟和成熟的DC与培养物和小鼠中的免疫物进行比较时，观察到的Pr降低免疫反应的增强> 100倍。使用MGF-OR HGF-转基因小鼠在表皮和真皮中的CL.6）在稳定状态下，使用DEM-205抗体抗原抗原抗原抗原抗原的ToLEN特异性Tet B细胞显示了toLe tole tementritic细胞指示是由于IL-2在没有IFN-I'M产生的情况下暂时增殖后的特定T细胞所致。