Impaired generation of CD8+ thymocytes in Ets-1-deficient mice

The Ets family of transcription factors function as key regulators of multiple aspects of immune cell development and function. To date, Ets-1 has been implicated in regulating early stages of thymic maturation and lymphocyte function and homeostasis. This report describes a novel role for Ets-1 in supporting later stages of thymic selection, in that positive selection of MHC class I-restricted CD4(+)CD8(+) double-positive thymocytes is markedly inhibited in mice expressing a hypomorphic allele of Ets-1. This effect is thymocyte intrinsic, as Ets-1 mutant thymocytes fail to efficiently generate CD8(+) single-positive thymocytes in mixed bone marrow chimeric backgrounds. Although peripheral CD8(+) T cells are present in Ets-1 mutant mice, both CD4(+) and CD8(+) subsets contain an elevated proportion of cells with an effector memory (CD62L(-)CD44(+)) phenotype. In addition, while thymic expression of Thy1 is relatively normal, peripheral T cells isolated from Ets-1 mutant mice display a striking loss of Thy1 expression. These data identify Ets-1 as a key transcription factor regulating thymocyte positive selection and lineage commitment of MHC class I-restricted thymocytes.