Myeloid dendritic cells and lymphoid dendritic cells

树突状细胞(DCs)是由表型和功能不同的群体组成的。这种异质性不仅归因于成熟阶段的差异，也归因于前体细胞来源的差异。在本研究中，我们对树突状细胞的分化和成熟与其作为强大的抗原提呈细胞的功能进行了实验研究，得到了以下结果：1)当注射荧光微球时，诱导进入注射部位的单核细胞吞噬了微球。其中大部分为巨噬细胞，但约有25%迁移到引流淋巴结内，表现为未成熟树突状细胞表型。微球转运细胞与常驻皮肤DC不同，在单核细胞缺陷OP/OP小鼠中，这种转运减少了85%以上。2)由于TH…，人外周血单个核细胞谱系中的CD11c^+CD1^+细胞是表皮朗格汉斯细胞的直接前体。3)β样树突状细胞产生的I型干扰素(α/β)对浆细胞样树突状细胞的自发成熟有明显的抑制作用。尽管干扰素-α/β和干扰素-γ均可诱导CD11c+DC表面MHC-II类分子和多种共刺激分子的表达上调，但干扰素-α/β不能诱导IL-12的产生，而是促进IL-10的产生。此外，干扰素-α/β阻断了干扰素-γ的作用，并使树突状细胞向Th0和/或Th2偏向T细胞活化。内吞蛋白抗原被递送到晚期内小体/溶酶体室(MIIC)，但除非DC暴露于炎症介质，否则MHC-多肽复合体不会形成。然而，一旦受到刺激，MHC-多肽复合体就会通过CIIV与MHC I类分子和共刺激分子一起运输到细胞表面，MHC和共刺激分子仍然聚集在一起。成熟DC向MHC II类分子负载抗原性货物的能力增强促成了&GT；将未成熟和成熟的DC作为免疫佐剂在培养和小鼠体内进行比较，观察到随后的初始免疫应答增强了100倍。5)表皮朗格汉斯细胞是原位最长寿的树突状细胞之一，通过使用MGF或HGF转基因小鼠吞噬表皮和真皮中的角蛋白颗粒，发现表皮朗格汉斯细胞持续迁移到引流淋巴结。6)在稳定状态下，持续从周围组织迁移的T区树突状细胞通过使用DEC-205抗体靶向抗原诱导抗原特异性T细胞的免疫耐受。耐受性的诱导是由于IL-2短暂增殖后特异性T细胞被删除，而不产生干扰素-γ。这一步被同时给予抗CD40单抗刺激具有抗原的树突状细胞所阻断。较少

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