CHARACTERIZATION OF RECENT THYMIC EMIGRANTS

胸腺在外周I细胞的建立和维持中起主要作用 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 (Rtes)已在对照条件下转基因绿色荧光蛋白(GFP)的小鼠中标记 RAG2启动子。GFP在预期的发育阶段开始表达，但GFP RAG2表达消失后，信号仍然存在。得到的GFP外周T细胞是 RTES，胸腺切除一周内消失。最近的数据显示，GFPhl外周T 淋巴样周围的细胞经历表型成熟和功能成熟。在RTE内 人群中，CD4/CD8比值较高，CD24表达较高，Qa-2表达较低 而不是更成熟的外周T细胞。CD8+RTE含有一半预期的细胞溶解前体， 在没有外源性IL-2的情况下，TCR交联后，CD4+RTE的增殖能力较差。关注的焦点之一 本研究旨在探讨淋巴组织中rtes的持续成熟 外周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MHC分子和IL-7是否是继续成熟所必需的 淋巴组织外周血中的CD4+和CD8+T细胞存活。此外，TCR曲目 将与成熟的外围同行进行分析和比较，并将 根据TCR判断RTE是否相互竞争成熟信号 专一性。另一个重点将是定义具有以下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细胞的产生的影响 T细胞的长期记忆。

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.