CHARACTERIZATION OF RECENT THYMIC EMIGRANTS

最近胸腺移民的特征

• 批准号: 7191610
• 负责人: Pamela J Fink
• 金额: $ 35.94万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7191610
• 关键词: Adult; Animals; Antibodies; Antigens; CD28 gene; CD4 Positive T Lymphocytes; CD4/CD8 ratio procedure; CD8B1 gene; Cell Differentiation process; Cell Maturation; Cell Survival; Cells; Class; Complement; Cytokine Receptors; Data; Defect; Dependence; Development; Doctor of Philosophy; Emigrant; Event; Generations; Green Fluorescent Proteins; Injection of therapeutic agent; Interleukin-2; Interleukin-7; Investigation; Laboratories; Life; Ligands; Localized; Longevity; Lymphoid; Lymphopenia; MHC Class I Genes; MHC Class II Genes; Maintenance; Mature T-Lymphocyte; Mediator of activation protein; Molecular; Mus; Nature; Numbers; Peripheral; Phenotype; Phosphorylation; Play; Population; Process; Proliferating; Proteins; Regulation; Research Personnel; Role; Signal Transduction; Specificity; Staging; Surface Antigens; T memory cell; T-Lymphocyte; Testing; Thymectomy; Thymus Gland; Time; Transgenic Mice; Week; Work; base; chemokine receptor; crosslink; cytokine; design; in vivo; insight; novel; pathogen; programs; promoter; protein expression; research study; response

DESCRIPTION (provided by applicant): The thymus plays a major role in the establishment and maintenance of the peripheral T cell pool throughout the lifespan of the animal. In work from this laboratory, recent thymic emigrants (RTEs) have been marked in mice transgenic for green fluorescent protein (GFP) under the control of the RAG2 promoter. GFP expression initiates at the expected developmental stage, but the GFP signal lingers after RAG2 expression is extinguished. The resulting GFP peripheral T cells are RTEs, disappearing within one week of thymectomy. Recent data show that GFPhl peripheral T cells undergo phenotypic and functional maturation in the lymphoid periphery. Within the RTE population, the CD4:CD8 ratio is higher, CD24 expression is higher, and Qa-2 expression is lower than on more mature peripheral T cells. CD8+ RTEs contain half the expected cytolytic precursors, and without exogenous IL-2, CD4+ RTEs proliferate poorly upon TCR crosslinking. One focus of the present investigation is to explore whether the continued maturation of RTEs in the lymphoid periphery is a selective process, requiring chemokine/receptor or TCR/ligand interactions. These experiments determine whether MHC molecules and IL-7 are required for the continued maturation and survival of CD4+ and CD8* RTEs in the lymphoid periphery. Furthermore, the TCR repertoire of RTEs will be analyzed and compared with that of their mature peripheral counterparts, and it will be determined whether RTEs compete with each other for maturation signals on the basis of TCR specificity. An additional focus will be to define the basis for the functional defects that characterize RTEs and the impact of these defects on the induction of T cell tolerance and the generation of long-term T cell memory.

描述（由申请人提供）：在动物的整个生命周期中，胸腺在外周T细胞池的建立和维持中起着重要作用。本实验室在RAG2启动子的控制下，在转基因绿色荧光蛋白（GFP）的小鼠中标记了最近的胸腺移植物（rte）。GFP在预期的发育阶段开始表达，但在RAG2表达消失后，GFP信号仍然存在。由此产生的GFP外周T细胞是rte，在胸腺切除术后一周内消失。最近的数据显示，GFPhl外周T细胞在淋巴样外周经历表型和功能成熟。在RTE人群中，CD4:CD8比值较高，CD24表达较高，Qa-2表达低于更成熟的外周T细胞。CD8+ rte含有一半预期的细胞溶解前体，并且没有外源性IL-2， CD4+ rte在TCR交联时增殖不良。本研究的一个重点是探讨淋巴样周围rte的持续成熟是否是一个选择性过程，需要趋化因子/受体或TCR/配体相互作用。这些实验确定了淋巴细胞周围CD4+和CD8* rte的持续成熟和存活是否需要MHC分子和IL-7。此外，我们将分析rte的TCR库，并将其与成熟外周细胞的TCR库进行比较，并根据TCR特异性确定rte是否会在成熟信号方面相互竞争。另一个重点将是定义rte特征的功能缺陷的基础，以及这些缺陷对诱导T细胞耐受性和产生长期T细胞记忆的影响。