Cutting Edge: Rag deletion in peripheral T cells blocks TCR revision

J Immunol. 2010 Jun 1;184(11):5964-8. doi: 10.4049/jimmunol.1000876. Epub 2010 Apr 30.

Abstract

Mature CD4(+)Vbeta5(+) T cells that recognize a peripherally expressed endogenous superantigen are tolerized either by deletion or TCR revision. In Vbeta5 transgenic mice, this latter tolerance pathway results in the appearance of CD4(+)Vbeta5(-)TCRbeta(+) T cells, coinciding with Rag1, Rag2, and TdT expression and the accumulation of V(beta)-DJ(beta) recombination intermediates in peripheral CD4(+) T cells. Because postthymic RAG-dependent TCR rearrangement has remained controversial, we sought to definitively determine whether TCR revision is an extrathymic process that occurs in mature peripheral T cells. We show in this study that Rag deletion in post-positive selection T cells in Vbeta5 transgenic mice blocks TCR revision in vivo and that mature peripheral T cells sorted to remove cells bearing endogenous TCRbeta-chains can express newly generated TCRbeta molecules in adoptive hosts. These findings unambiguously demonstrate postthymic, RAG-dependent TCR rearrangement and define TCR revision as a tolerance pathway that targets mature peripheral CD4(+) T cells.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Separation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology*
  • Flow Cytometry
  • Gene Rearrangement, T-Lymphocyte / genetics*
  • Immune Tolerance / genetics
  • Immune Tolerance / immunology
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA-Binding Proteins
  • Rag2 protein, mouse
  • Receptors, Antigen, T-Cell