Id3 restricts the developmental potential of gamma delta lineage during thymopoiesis

J Immunol. 2009 May 1;182(9):5306-16. doi: 10.4049/jimmunol.0804249.

Abstract

Most T cell progenitors develop into the alphabeta T cell lineage with the exception of a small fraction contributing to the gammadelta lineage throughout postnatal life. T cell progenitors usually commit to the alphabeta lineage upon the expression of a fully rearranged and functional TCRbeta gene, and most cells that fail to produce a functional TCRbeta-chain will die instead of adopting the alternative gammadelta T cell fate. What prevents these cells from continuing TCRgamma rearrangement and adopting the gammadelta T cell fate is not known. In this study, we show that functional loss of Id3 results in a significant increase of gammadelta T cell production from progenitor cells undergoing TCRbeta rearrangement. The enhanced gammadelta T cell development correlated with increased TCRgamma gene rearrangement involving primarily Vgamma1.1 in Id3 deficient mice. We further show that Id3 deficiency promotes gammadelta T cell production in a manner independent of TCRbeta-chain expression. Our data indicates that Id3 suppresses Vgamma1.1 rearrangement and gammadelta lineage potential among T cell progenitors that have completed TCRbeta gene rearrangement without producing a functional TCRbeta protein.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cell Lineage / genetics
  • Cell Lineage / immunology*
  • Cells, Cultured
  • Gene Knockout Techniques
  • Gene Rearrangement, delta-Chain T-Cell Antigen Receptor* / genetics
  • Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor* / genetics
  • Inhibitor of Differentiation Proteins / deficiency
  • Inhibitor of Differentiation Proteins / genetics
  • Inhibitor of Differentiation Proteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Mutant Strains
  • Receptors, Antigen, T-Cell, gamma-delta / antagonists & inhibitors*
  • Receptors, Antigen, T-Cell, gamma-delta / biosynthesis*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism

Substances

  • Inhibitor of Differentiation Proteins
  • Receptors, Antigen, T-Cell, gamma-delta
  • Idb3 protein, mouse