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Immunity. 2012 Mar 23;36(3):348-61. doi: 10.1016/j.immuni.2012.02.010. Epub 2012 Mar 15.

E protein transcription factors are required for the development of CD4(+) lineage T cells.

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1
Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.

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.

PMID:
22425249
PMCID:
PMC3431168
DOI:
10.1016/j.immuni.2012.02.010
[Indexed for MEDLINE]
Free PMC Article

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