Physiological and cell biological studies on dendritic cells

树突状细胞的生理和细胞生物学研究

基本信息

批准号：
10044268
负责人：
INABA Kayo
金额：
$ 4.93万
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：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

Antigen uptake, processing and presentation by dendritic cells (DCs) have become amenable to cell biological approaches. The critical events occur in DCs that are undergoing development and maturation in response to inflammatory stimuli. The aim of this project is to define developmental stages and to elucidate regulatory mechanisms of antigen processing in immunostimulatory dendritic cells. The following results are obtained.1) DCs ate unusually efficient at forming MHC-peptide complexes from phagocytosed cells, some 1-10 thousand times more efficiently than an exposure to preprocessed peptide. A comparable phenomenon is observed in vivo when short-lived migratory DCs migrate via afferent lymphatics to the T cell areas of the lymph nodes.2) After phagocytosing injected microspheres, about 25% of inflammatory monocytes migrated to the T area of draining node, where they expressed dendritic cell-restricted markers and high levels of costimulatory molecules.3) Fractalkine/neurotactin and … More MDC are isolated from mouse bone marrow-derived DC cDNA libraries by the signal sequence trap method. Both chemokines are expressed by DC differentiated from bone marrow precursors cells in vitro and mature DCs from tissues, and constitutively produced by DCs in T area to attract T cells.4) Based on the relative expression of CD11c and CD1a, we have identified three fractions of DCs in human peripheral blood. A major population expressing CD1a and CD11c is demonstrated to be immediate precursors of epidermal Langerhans cells. A minor fraction (CD1a-CD11c-) is identified as plasmacytoid T cells, which are supposed to be lymphoid-lineage DCs.5) Immature dendritic cells internalize antigens into lysosomal compartments rich in MHC II molecules. The capacity of MHC-rich lysosomes to mediate the formation of MHC II-peptide complexes is strictly controlled during dendritic cell differentiation, helping to coordinate antigen acquisition and inflammatory stimuli with formation of ligands for the T cell receptor. Less

树突状细胞 (DC) 的抗原摄取、加工和呈递已变得适合于细胞生物学方法，这些关键事件发生在响应炎症刺激而进行发育和成熟的 DC 中。阐明了免疫刺激性树突状细胞中抗原加工的调节机制，获得了以下结果。1) DC 在从被吞噬的细胞形成 MHC-肽复合物方面异常有效。当短命的迁移 DC 通过传入淋巴管迁移到淋巴结的 T 细胞区域时，体内观察到的效率比暴露于预处理的肽高 1-10,000 倍。2) 吞噬注射的微球后，约 25 倍。 %的炎性单核细胞迁移到引流结的T区，在那里表达树突状细胞限制性标记物和高水平的共刺激分子。3) Fractalkine/neurotactin 和 MDC 通过信号序列捕获法从小鼠骨髓来源的 DC cDNA 文库中分离出来，这两种趋化因子均由体外骨髓前体细胞分化的 DC 和组织中成熟的 DC 表达，并由 DC 组成型产生。 4）根据CD11c和CD1a的相对表达，我们确定了人外周血中表达CD1a和CD11a的主要DC群体的三个部分。 CD11c 被证明是表皮朗格汉斯细胞的直接前体。一小部分 (CD1a-CD11c-) 被鉴定为浆细胞样 T 细胞，它们被认为是淋巴谱系 DC。5) 未成熟的树突状细胞将抗原内化到富含溶酶体的区室中。 MHC II 分子。富含 MHC 的溶酶体介导 MHC II-肽复合物形成的能力在过程中受到严格控制。树突状细胞分化，有助于协调抗原获取和炎症刺激与 T 细胞受体配体的形成。