Thymocyte maturation is regulated by the activity of the helix-loop-helix protein, E47

J Exp Med. 1999 Dec 6;190(11):1605-16. doi: 10.1084/jem.190.11.1605.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Survival
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Flow Cytometry
  • Gene Dosage
  • Helix-Loop-Helix Motifs
  • Lymphocyte Activation*
  • Lymphoma, T-Cell / immunology
  • Major Histocompatibility Complex
  • Mice
  • Mice, Knockout
  • Receptors, Antigen, T-Cell, alpha-beta / immunology
  • T-Lymphocytes / immunology*
  • TCF Transcription Factors
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors*
  • Transfection
  • Tumor Cells, Cultured
  • beta 2-Microglobulin / deficiency
  • beta 2-Microglobulin / genetics
  • beta 2-Microglobulin / physiology

Substances

  • DNA-Binding Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • TCF Transcription Factors
  • Tcf7l1 protein, mouse
  • Transcription Factor 7-Like 1 Protein
  • Transcription Factors
  • beta 2-Microglobulin