CHARACTERIZATION OF RECENT THYMIC EMIGRANTS

描述（由申请方提供）：胸腺在动物整个生命周期中对外周T细胞池的建立和维持起主要作用。在本实验室的工作中，在RAG 2启动子控制下的绿色荧光蛋白（GFP）转基因小鼠中标记了最近的胸腺移行细胞（RTE）。GFP表达在预期的发育阶段开始，但GFP信号在RAG 2表达消失后徘徊。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细胞在淋巴外周中经历表型和功能成熟。在RTE群体中，与更成熟的外周T细胞相比，CD 4：CD 8比率更高，CD 24表达更高，Qa-2表达更低。CD 8 + RTE含有预期的细胞溶解前体的一半，并且在没有外源性IL-2的情况下，CD 4 + RTE在TCR交联时增殖不良。本研究的一个重点是探讨淋巴外周中RTEs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MHC分子和IL-7是否是淋巴外周中CD 4+和CD 8 * RTE持续成熟和存活所必需的。此外，将分析RTE的TCR库并与其成熟外周对应物的TCR库进行比较，并将确定RTE是否基于TCR特异性彼此竞争成熟信号。另一个重点将是定义的功能缺陷的基础上，RTEs和这些缺陷的T细胞耐受性的诱导和长期T细胞记忆的产生的影响。

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.