Cortical epithelial cells in the selection and maturation of CD8 T cells

描述（申请人提供）：胸腺是T细胞发育的专门器官。在胸腺内，皮质上皮细胞在产生特异性和功能合适的T细胞中起着至关重要的作用。在这个项目中，我们将研究在皮质上皮细胞中唯一表达的基因25t的作用，该基因参与蛋白水解，并且是CD8 T细胞阳性选择所必需的。我们将进一步定义和研究关键的皮质上皮细胞鉴定基因，通过创建报告小鼠来促进这些细胞在体内的纯化或消耗。我们还将确定25T和其他基因是否在T细胞发育受损的情况下发生改变，并确定这些基因的操作是否可用于支持体外T细胞重建。该建议的另一个重点是定义在正选择之后发生的功能成熟所需的遗传变化。具体来说，我们将确定：在半成熟到成熟的SP转变过程中发生了哪些基因变化，哪些变化对增殖能力的发展至关重要，以及增殖能力是否需要特定的基质细胞相互作用

DESCRIPTION (provided by applicant): The thymus is a specialized organ for the development of T cells. Within the thymus, cortical epithelial cells play a crucial role in the generation of T cells with appropriate specificity and function. In this project, we will study the role of a gene expressed uniquely in cortical epithelial cells, 25t, which is involved in proteolysis and is required for positive selection of CD8 T cells. We will further define and study key cortical epithelial cell identify genes by creating reporter mice to facilitate the purification or depletion of these cells in vivo. We will also determine if 25T and other genes are altered in situations where T cell development is impaired, and determine if manipulation of these genes can be used to support T cell reconstitution in vitro. Another focus of this proposal is to define the genetic changes required for the functional maturation that occurs after positive selection. Specifically, we will determine: what gene changes occur at the semi-mature to mature SP transition, which changes are critical for development of proliferation competence, and if specific stromal cell interactions are required for competence