ANTIGEN PRESENTING CELLS IN EPITHELIA

CD4+T淋巴细胞的活化是MOST发生发展所必需的 免疫反应，需要特殊的抗原提呈细胞(APC)。 朗格汉斯细胞(LC)可能是第一个遇到抗原的APC 在常规免疫反应中，因为大多数病原体进入人体 通过表皮，通过吸入或摄入。LC被诱使离开 局部创伤所致的上皮细胞损伤。它们通过传入进行迁移 淋巴管进入引流的淋巴结，在那里它们激活初始T细胞 上皮细胞中遇到的抗原。其中所涉及的信号 他们的迁徙没有得到很好的描述。这个项目的目标是 确定诱导LC迁移到的上皮细胞和信号 淋巴结。这项研究的最终目的是开发方法 用于调节本地站点中的LC迁移。 将使用两种突变动物模型来分析LC的迁移。 突变的小鼠携带着独立的基因缺陷，这两种缺陷都会导致LC 转移到淋巴结。这项建议的具体目的是1) 描述第一个突变体中LC迁移的缺陷；2) 建立小鼠LC影响因素的体外检测系统 迁移；3)刻画第二类LC迁移中的缺陷 突变；以及4)建立一个体外系统来确定因子 控制人类LC迁移。

Activation of CD4+ T lymphocytes is necessary for the development of most immune responses and requires specialized antigen-presenting cells (APC). Langerhans cells (LC) are probably the first APCs to encounter antigen during a conventional immune response, as most pathogens enter the body via the epidermis, by inhalation or ingestion. LC are induced to leave epithelia as a result of local trauma. They migrate via afferent lymphatics to the draining lymph node, where they activate naive T cells to the antigens encountered in the epithelium. The signals involved in their migration are poorly characterized. The goal of this project is to determine the epithelial cells and signals that induce LC to migrate to lymph nodes. The ultimate purpose of this research is to develop methods for modulating LC migration in local sites. Two mutant animal models will be used for the analysis of LC migration. The mutant mice carry independent genetic defects both of which abolish LC migration to lymph nodes. The Specific Aims of this proposal are 1) to characterize the defect in the migration of LC in the first mutant; 2) to develop an in vitro system to determine the factors controlling murine LC migration; 3) to characterize the defect in LC migration in the second mutant; and 4) to develop an in vitro system to determine the factors controlling human LC migration.