Abstract
The E2A proteins, E12 and E47, are required for progression through multiple developmental pathways, including early B and T lymphopoiesis. Here, we provide in vitro and in vivo evidence demonstrating that E47 activity regulates double-positive thymocyte maturation. In the absence of E47 activity, positive selection of both major histocompatibility complex (MHC) class I- and class II-restricted T cell receptors (TCRs) is perturbed. Additionally, development of CD8 lineage T cells in an MHC class I-restricted TCR transgenic background is sensitive to the dosage of E47. Mice deficient for E47 display an increase in production of mature CD4 and CD8 lineage T cells. Furthermore, ectopic expression of an E2A inhibitor helix-loop-helix protein, Id3, promotes the in vitro differentiation of an immature T cell line. These results demonstrate that E2A functions as a regulator of thymocyte positive selection.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cell Survival
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Flow Cytometry
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Gene Dosage
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Helix-Loop-Helix Motifs
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Lymphocyte Activation*
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Lymphoma, T-Cell / immunology
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Major Histocompatibility Complex
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Mice
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Mice, Knockout
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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T-Lymphocytes / immunology*
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TCF Transcription Factors
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Transcription Factor 7-Like 1 Protein
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Transcription Factors*
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Transfection
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Tumor Cells, Cultured
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beta 2-Microglobulin / deficiency
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beta 2-Microglobulin / genetics
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beta 2-Microglobulin / physiology
Substances
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DNA-Binding Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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TCF Transcription Factors
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Tcf7l1 protein, mouse
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Transcription Factor 7-Like 1 Protein
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Transcription Factors
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beta 2-Microglobulin