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The Journal of Immunology, 2006, 177: 905-912.
Copyright © 2006 by The American Association of Immunologists

Impaired Generation of CD8+ Thymocytes in Ets-1-Deficient Mice1

James L. Clements2,*, Shinu A. John{dagger} and Lee Ann Garrett-Sinha{dagger}

* Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263; and {dagger} Department of Biochemistry, State University of New York, Buffalo, NY 14241

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.


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The JI 2006 177: 767-768. [Full Text]  



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