CHARACTERIZATION OF RECENT THYMIC EMIGRANTS

描述(申请人提供)：胸腺在动物的整个生命周期中，在建立和维持外周T细胞池中起着重要作用。在该实验室的工作中，在RAG2启动子的控制下，最近的胸腺移民(RTES)已经在转基因绿色荧光蛋白(GFP)的小鼠中进行了标记。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RTES，在胸腺切除后一周内消失。最近的数据显示，GFPh1外周T细胞在淋巴外周经历了表型和功能的成熟。在RTE人群中，与更成熟的外周T细胞相比，CD4/CD8比率更高，CD24表达更高，Qa-2表达更低。CD8+RTE含有一半的预期溶细胞前体，如果没有外源性IL-2，则TCR交联后，CD4+RTE的增殖能力很差。目前研究的一个重点是探索淋巴样外周的RTES的持续成熟是否是一个选择性的过程，需要趋化因子/受体或TCR/配体的相互作用。这些实验确定是否需要MHC分子和IL-7来继续成熟和生存淋巴样外周细胞中的CD4+和CD8*rte。此外，RTE的TCR谱将被分析并与其成熟的外周同行进行比较，并将根据TCR的特异性来确定RTE是否相互竞争成熟信号。另一个重点将是确定以RTE为特征的功能缺陷的基础，以及这些缺陷对T细胞耐受的诱导和T细胞长期记忆的产生的影响。

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.