Overexpression of the Helix-Loop-Helix protein Id2 blocks T cell development at multiple stages

Mol Immunol. 1999 Jun;36(8):491-503. doi: 10.1016/s0161-5890(99)00071-1.

Abstract

The Id proteins are inhibitors of basic-Helix-Loop-Helix transcription factor function that have been implicated in the control of cell differentiation and proliferation. To study the role of Id proteins in the control of T cell development, we generated transgenic mice that overexpress the Id2 protein in thymocytes. We detect a significant expansion of the early CD4(-)CD8(+)TCR(-) thymocyte stage and a depletion of the thymocytes of the subsequent developmental stages. These data indicate that the overexpression of Id2 leads to a stage-specific developmental block early in thymopoiesis. In addition, progeny mice from five of the six Id2 transgenic founder lines succumb to aggressive T cell hyperproliferation that resembles lymphoma. Thus, overexpression of the Id2 protein has profound effects on T cell development and oncogenesis, consistent with the hypothesis that the bHLH proteins play critical roles in these processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / cytology
  • CD8-Positive T-Lymphocytes / immunology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Division / genetics
  • Cell Division / immunology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / immunology*
  • Female
  • Helix-Loop-Helix Motifs / genetics
  • Helix-Loop-Helix Motifs / immunology
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology
  • Inhibitor of Differentiation Protein 2
  • Lymphocyte Activation / genetics
  • Lymphoma, T-Cell / etiology
  • Lymphoma, T-Cell / genetics
  • Lymphoma, T-Cell / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Transgenic
  • Repressor Proteins / genetics*
  • Repressor Proteins / immunology*
  • Spleen / cytology
  • Spleen / immunology
  • T-Lymphocyte Subsets / cytology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Transcription Factors*

Substances

  • DNA-Binding Proteins
  • Idb2 protein, mouse
  • Inhibitor of Differentiation Protein 2
  • Repressor Proteins
  • Transcription Factors