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: The first checkpoint in T cell development, [beta] selection, has remained incompletely characterized for lack of specific surface markers. We show that CD27 is upregulated in DN3 thymocytes initiating [beta] selection, concomitant with intracellular TCR-[beta] expression. Clonal analysis determined that CD27high DN3 cells generate CD4 CD8 progeny with more than 90% efficiency, faster and more efficiently than the CD27low majority. CD27 upregulation also occurs in [gamma][delta]-selected DN3 thymocytes in TCR-[beta]-/- mice and in IL2-GFP transgenic reporter mice where GFP marks the earliest emerging TCR-[gamma][delta] cells from DN3 thymocytes. With CD27 to distinguish pre- and postselection DN3 cells, a detailed gene expression analysis defined regulatory changes associated with checkpoint arrest, with [beta] selection, and with [gamma][delta] selection. [gamma][delta] selection induces higher CD5, Egr, and Runx3 expression as compared to [beta] selection, but it triggers less proliferation. Our results also reveal differences in Notch/Delta dependence at the earliest stages of divergence between developing [alpha][beta] and [gamma][delta] T-lineage cells.

(C) 2006Elsevier, Inc.