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

皮质上皮细胞在 CD8 T 细胞的选择和成熟中的作用

基本信息

批准号：
8051805
负责人：
Kristin A. Hogquist
金额：
$ 36.56万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-04-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8051805
关键词：
Antigen Receptors Antigens Apoptosis Biological Testing CD4 Positive T Lymphocytes CD8B1 gene CTSL gene Candidate Disease Gene Cathepsin L Cell Communication Cells Competence Development Epithelial Cells Generations Genes Health Histocompatibility Antigens Class I In Vitro Knock-in Mouse Knockout Mice Knowledge MHC binding peptide Mature Thymocyte Microarray Analysis Molecular Mus Mutation Nature Organ Peptide Hydrolases Peptides Play Predisposition Proliferating Proteolysis Reporter Role Signaling Pathway Gene Specificity Staging Stromal Cells System T cell differentiation T-Cell Development T-Cell Receptor T-Lymphocyte Testing Therapeutic Uses Thymus Gland Time Tissues Transgenic Organisms base cytokine in vivo loss of function mouse model multicatalytic endopeptidase complex novel peptide I progenitor reconstitution thymocyte tool

项目摘要

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 PUBLIC HEALTH RELEVANCE: The thymus is a specialized organ for the development of T cells. Within this organ, cortical epithelial cells play a crucial role in the generation of T cells with appropriate specificity and function. This application proposes to explore the molecular mechanisms by which cortical epithelial cells support T cell differentiation, and to exploit this knowledge in developing an in vitro T cell reconstitution system that can be used for therapeutic purposes.

描述（由申请人提供）：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具有适当特异性和功能的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独特表达的基因25t的作用，该基因参与蛋白水解，并且是CD8 T细胞的阳性选择所必需的。我们将进一步定义和研究关键的皮质上皮细胞识别基因，通过创建报告小鼠，以促进这些细胞在体内的纯化或耗尽。我们还将确定在T细胞发育受损的情况下25T和其他基因是否发生改变，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正向选择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SP从半成熟到成熟的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异性基质细胞相互作用。公共卫生相关性：胸腺是T细胞发育的专门器官。在这个器官中，皮质上皮细胞在产生具有适当特异性和功能的T细胞中起着至关重要的作用。本申请提出探索皮质上皮细胞支持T细胞分化的分子机制，并利用这一知识开发可用于治疗目的的体外T细胞重建系统。