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

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.

Pubmed ID: 22425249

Authors

  • Jones-Mason ME
  • Zhao X
  • Kappes D
  • Lasorella A
  • Iavarone A
  • Zhuang Y

Journal

Immunity

Publication Data

March 23, 2012

Associated Grants

  • Agency: NCI NIH HHS, Id: R01 CA153260
  • Agency: NIGMS NIH HHS, Id: R01 GM059638
  • Agency: NIGMS NIH HHS, Id: R01 GM059638-09A1
  • Agency: NIGMS NIH HHS, Id: R01 GM059638-10
  • Agency: NIGMS NIH HHS, Id: R01 GM059638-11
  • Agency: NIGMS NIH HHS, Id: R01 GM059638-12
  • Agency: NIGMS NIH HHS, Id: R01GM059638

Mesh Terms

  • Animals
  • Antigens, CD4
  • Basic Helix-Loop-Helix Transcription Factors
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cell Differentiation
  • Inhibitor of Differentiation Protein 2
  • Inhibitor of Differentiation Proteins
  • Interleukin-7 Receptor alpha Subunit
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Receptors, CCR7
  • Up-Regulation