Abstract
The double-positive (DP) to single-positive (SP) transition during T cell development is initiated by downregulation of the E protein transcription factors HEB and E2A. Here, we have demonstrated that in addition to regulating the onset of this transition, HEB and E2A also play a separate role in CD4(+) lineage choice. Deletion of HEB and E2A in DP thymocytes specifically blocked the development of CD4(+) lineage T cells. Furthermore, deletion of the E protein inhibitors Id2 and Id3 allowed CD4(+) T cell development but blocked CD8(+) lineage development. Analysis of the CD4(+) lineage transcriptional regulators ThPOK and Gata3 placed HEB and E2A upstream of CD4(+) lineage specification. These studies identify an important role for E proteins in the activation of CD4(+) lineage differentiation as thymocytes undergo the DP to SP transition.
Copyright © 2012 Elsevier Inc. All rights reserved.
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
Animals
-
Basic Helix-Loop-Helix Transcription Factors / deficiency
-
Basic Helix-Loop-Helix Transcription Factors / genetics
-
Basic Helix-Loop-Helix Transcription Factors / immunology*
-
CD4 Antigens / genetics
-
CD4-Positive T-Lymphocytes / cytology
-
CD4-Positive T-Lymphocytes / immunology*
-
CD4-Positive T-Lymphocytes / metabolism
-
CD8-Positive T-Lymphocytes / cytology
-
CD8-Positive T-Lymphocytes / immunology
-
CD8-Positive T-Lymphocytes / metabolism
-
Cell Differentiation / immunology
-
Inhibitor of Differentiation Protein 2 / deficiency
-
Inhibitor of Differentiation Protein 2 / genetics
-
Inhibitor of Differentiation Protein 2 / immunology
-
Inhibitor of Differentiation Proteins / deficiency
-
Inhibitor of Differentiation Proteins / genetics
-
Inhibitor of Differentiation Proteins / immunology
-
Interleukin-7 Receptor alpha Subunit / metabolism
-
Mice
-
Mice, 129 Strain
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Mice, Transgenic
-
Receptors, CCR7 / metabolism
-
Up-Regulation
Substances
-
Basic Helix-Loop-Helix Transcription Factors
-
CD4 Antigens
-
Ccr7 protein, mouse
-
Idb2 protein, mouse
-
Inhibitor of Differentiation Protein 2
-
Inhibitor of Differentiation Proteins
-
Interleukin-7 Receptor alpha Subunit
-
Receptors, CCR7
-
Tcf12 protein, mouse
-
Tcf3 protein, mouse
-
Idb3 protein, mouse