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.
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