Combined deletion of Id2 and Id3 genes reveals multiple roles for E proteins in invariant NKT cell development and expansion

J Immunol. 2013 Nov 15;191(10):5052-64. doi: 10.4049/jimmunol.1301252. Epub 2013 Oct 11.

Abstract

The invariant NKT (iNKT) cells represent a unique group of αβ T cells that have been classified based on their exclusive usage of the invariant Vα14Jα18 TCRα-chain and their innate-like effector function. Thus far, the transcriptional programs that control Vα14Jα18 TCRα rearrangements and the population size of iNKT cells are still incompletely defined. E protein transcription factors have been shown to play necessary roles in the development of multiple T cell lineages, including iNKT cells. In this study, we examined E protein functions in T cell development through combined deletion of genes encoding E protein inhibitors Id2 and Id3. Deletion of Id2 and Id3 in T cell progenitors resulted in a partial block at the pre-TCR selection checkpoint and a dramatic increase in numbers of iNKT cells. The increase in iNKT cells is accompanied with a biased rearrangement involving Vα14 to Jα18 recombination at the double-positive stage and enhanced proliferation of iNKT cells. We further demonstrate that a 50% reduction of E proteins can cause a dramatic switch from iNKT to innate-like γδ T cell fate in Id2- and Id3-deficient mice. Collectively, these findings suggest that Id2- and Id3-mediated inhibition of E proteins controls iNKT development by restricting lineage choice and population expansion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • CD4 Antigens / metabolism
  • CD8 Antigens / metabolism
  • Cell Differentiation
  • Cell Lineage
  • Cell Proliferation
  • Inhibitor of Differentiation Protein 2 / genetics*
  • Inhibitor of Differentiation Proteins / genetics*
  • Lymphocyte Count
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Natural Killer T-Cells / metabolism*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • CD4 Antigens
  • CD8 Antigens
  • Idb2 protein, mouse
  • Inhibitor of Differentiation Protein 2
  • Inhibitor of Differentiation Proteins
  • Receptors, Antigen, T-Cell, alpha-beta
  • Idb3 protein, mouse