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

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

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.

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