ANTIGEN PRESENTING CELLS IN EPITHELIA

CD 4 + T淋巴细胞的活化对于大多数癌症的发展是必要的。 免疫反应，需要专门的抗原呈递细胞（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，当大多数病原体进入人体时， 通过表皮，吸入或摄入。 LC被诱导离开 局部创伤导致的上皮细胞损伤 它们通过传入 淋巴结引流，在那里他们激活幼稚T细胞 与上皮细胞中遇到的抗原结合。 参与的信号 他们的移徙情况不太清楚。 该项目的目标是 确定上皮细胞和诱导LC迁移到 淋巴结 这项研究的最终目的是开发方法 用于调节局部位点中的LC迁移。 两种突变动物模型将用于LC迁移分析。 突变小鼠携带独立的遗传缺陷，这两种缺陷都消除了LC 转移至淋巴结。 本建议的具体目标是：（1） 表征第一突变体中LC迁移的缺陷; 2） 建立一个体外系统，以确定控制小鼠LC的因素 3）表征第二阶段LC迁移中的缺陷 突变体;和4）开发体外系统以确定因子 控制人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.