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Analysis of cutaneous Langerhans cells and dendritic cells.

皮肤朗格汉斯细胞和树突状细胞的分析。

基本信息

批准号：
08670950
负责人：
NAKAMURA Koichiro
金额：
$ 1.22万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
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

项目摘要

Murine epiermis conatins Langerhans cells(LC)and Thy-1+ dendritic epidermal T cells(DETC). In this report, 1)The mechanism of activation of LC and DETC in transgenic mice, 2)the ontogeny of DETC and thy-1+ dermal dendritic cells(DC), and 3)the effects of MCSF on LC activation were examined. 1)Transgenic(tg)mice were generated using construct containing a 2.1 Kb segment containing the promoter sequences of human K14 gene, as well as a cDNA encoding MCP-1. A dramatic increase in number of I-Aq positive cells was observed and an increase in the number of such cells in the dermis had Birbech granules. Enhanced contact hypersensitivity responses were observed in MCP-1tg mice, and a significant increase of the number of DETC was observed, when croton oil were applied as a sensitizer in MCP-1 tg mice., There was little enhancement of B7-1 and B7-2 on LC of MCP-1 tg mice compared with wt mice. These data indicate that efficiently activating mechanism in DC and DETC may exist in K14/MCP-1 mice, . and that MCP-1 may be important for the regulation of immunological function in skin.2)The ontogeny of DETC and thy-1+ dermal DC was examined using wt mice. DETC were already observed in day 16 embryo, and the number of gammadeltaTCR+ DETC increased gradually. The number of fetal thy-1+ dermal DC decreased gradually after day 16 embryo.3)The effects of cytokines on the costimualtory molecules in purified LC were examined. M-CSF significantly upregulared B7-1 and B7-2 expressions on purified LC by 12 hours culture.These data indicate that chemiokines like MCP-1 can influence the migration of LC and DETC,resulting in the modulation of cutaneous immune responses. The result concerning MCP-1 and M-CSF stronfgly suggests that LC and macrophages have some interaction during their differentiation processes.

小鼠表皮细胞含有朗格汉斯细胞（LC）和Thy-1+树突状表皮T细胞（DETC）。本研究探讨了转基因小鼠LC和DETC的激活机制，DETC和Thy-1+树突状细胞（DC）的个体发生，以及MCSF对LC激活的影响。1）使用包含含有人K14基因启动子序列的2.1Kb片段以及编码MCP-1的cDNA的构建体产生转基因（tg）小鼠。观察到I-Aq阳性细胞数量的急剧增加，并且真皮中此类细胞数量的增加具有Birbech颗粒。当巴豆油作为致敏剂应用于MCP-1 tg小鼠时，在MCP-1 tg小鼠中观察到增强的接触超敏反应，并且观察到DETC数量的显著增加。与野生型小鼠相比，B7-1和B7-2对MCP-1 tg小鼠的LC几乎没有增强作用。提示K14/MCP-1小鼠可能存在DC和DETC的有效激活机制。MCP-1可能在皮肤免疫功能的调节中起重要作用。2）使用wt小鼠检测DETC和thy-1+真皮DC的个体发育。在16天胚胎中已观察到DETC，γ δ TCR + DETC的数量逐渐增加。胎龄16 d后，胎鼠真皮中Thy-1+ DC的数量逐渐减少。3）检测细胞因子对纯化的LC中共刺激分子的影响。M-CSF可显著上调纯化LC表面B7-1和B7-2的表达，提示MCP-1等趋化因子可影响LC和DETC的迁移，从而调节皮肤免疫反应。MCP-1和M-CSF的结果表明，LC和巨噬细胞在分化过程中存在一定的相互作用。