TCRgamma silencing during alphabeta T cell development depends upon pre-TCR-induced proliferation

J Immunol. 2006 Nov 1;177(9):6038-43. doi: 10.4049/jimmunol.177.9.6038.

Abstract

During thymus development, immature T cells become committed to two distinct lineages based upon expression of alphabeta or gammadelta TCR. In the alphabeta lineage, developing thymocytes progressively extinguish transcription of the TCRgamma genes by a poorly understood process known as gamma silencing. We show that alphabeta lineage thymocytes in mice lacking a functional pre-TCR undergo limited proliferation and fail to silence TCRgamma genes during development. Stimulation of pre-TCR-deficient immature thymocytes with anti-CD3 Abs does not directly down-regulate TCRgamma transcription but restores TCRgamma silencing following proliferation. Collectively our data reveal an important role for pre-TCR induced proliferation in activating the TCRgamma silencer in alphabeta lineage thymocytes, a process that may reinforce alphabeta or gammadelta lineage commitment.

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • CD3 Complex / immunology
  • Cell Lineage / genetics
  • Cell Proliferation
  • Gene Silencing*
  • Mice
  • Receptors, Antigen, T-Cell, alpha-beta / agonists
  • Receptors, Antigen, T-Cell, alpha-beta / analysis*
  • Receptors, Antigen, T-Cell, gamma-delta / agonists
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Silencer Elements, Transcriptional / genetics
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • Thymus Gland / cytology
  • Thymus Gland / growth & development*
  • Thymus Gland / immunology

Substances

  • Antibodies
  • CD3 Complex
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta