Analysis of cutaneous Langerhans cells and dendritic cells.

小鼠表皮细胞包括郎格汉斯细胞(LC)和Thy-1+树突状表皮T细胞(DETC)。本文研究了转基因小鼠LC和DETC的激活机制，DETC和THY-1+真皮树突状细胞(DC)的个体发育，以及MCSF对LC激活的影响。1)利用含有人K14基因启动子序列的2.1kb片段和编码单核细胞趋化蛋白-1(MCP-1)的cDNA构建了转基因(TG)小鼠。I-AQ阳性细胞数量显著增加，真皮内I-AQ阳性细胞数量增加有Birbech颗粒。B7-1和B7-2对MCP-1TG小鼠的触敏反应增强，DETC数显著增加，而B7-1和B7-2对小鼠LC的促进作用较小。提示K14/MCP-1小鼠DC和DETC可能存在有效的激活机制。MCP-1在皮肤免疫功能调节中可能起重要作用。2)用小鼠观察DETC和THY-1+真皮DC的个体发育。胚胎第16天已有DETC出现，GAMADELTA TCR+DETC数量逐渐增多。胚胎16天后胎儿Thy-1+真皮DC数量逐渐减少。3)检测细胞因子对纯化LC中共刺激分子的影响。经12小时培养，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，从而调节皮肤免疫应答。对单核细胞趋化蛋白-1和巨噬细胞集落刺激因子的研究结果表明，LC和巨噬细胞在分化过程中存在一定的相互作用。

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.