CHARACTERIZATION OF RECENT THYMIC EMIGRANTS

最近胸腺移民的特征

• 批准号: 7584702
• 负责人: Pamela J Fink
• 金额: $ 5.98万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-15 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7584702
• 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; 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

The thymus plays amajor role in the establishment andmaintenance oftheperipheral I 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.

胸腺在外周I细胞的建立和维持中起重要作用 在动物的整个生命周期中。在这个实验室的工作中，最近的胸腺移民 在对照下，在转绿色荧光蛋白（GFP）基因的小鼠中标记了RTE RAG 2启动子GFP表达在预期的发育阶段开始，但GFP表达在预期的发育阶段开始。 信号在RAG 2表达消失后仍然存在。所得到的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 细胞在淋巴外周中经历表型和功能成熟。在RTE内 CD 4：CD 8比值较高，CD 24表达较高，Qa-2表达较低 而不是更成熟的外周T细胞。CD 8 + RTEs含有预期溶细胞前体的一半， 而在没有外源性IL-2的情况下，CD 4 + RTEs在TCR交联时增殖不良。的一个重点 本研究旨在探讨淋巴细胞中RTEs的持续成熟是否 外周是一个选择性过程，需要趋化因子/受体或TCR/配体相互作用。这些 实验确定MHC分子和IL-7是否是持续成熟所必需的 以及淋巴外周中CD 4+和CD 8 * RTEs的存活。此外，TCR库 的RTE将进行分析，并与其成熟的周边同行进行比较，它将 确定RTE是否基于TCR相互竞争成熟信号 的特异性另一个重点将是定义功能缺陷的基础， RTE和这些缺陷对T细胞耐受诱导和免疫耐受产生的影响。 长期T细胞记忆