Thymic Selection of CD4+CD25+ Regulatory T Cells Induced by an Agonist Self-Peptide

Nat Immunol. 2001 Apr;2(4):301-6. doi: 10.1038/86302.

Abstract

Despite accumulating evidence that regulatory T cells play a crucial role in preventing autoimmunity, the processes underlying their generation during immune repertoire formation are unknown. We show here that interactions with a single self-peptide can induce thymocytes that bear an autoreactive T cell receptor (TCR) to undergo selection to become CD4+CD25+ regulatory T cells. Selection of CD4+CD25+ thymocytes appears to require a TCR with high affinity for a self peptide because thymocytes that bear TCRs with low affinity do not undergo selection into this pathway. Our findings indicate that specificity for self-peptides directs the selection of CD4+CD25+ regulatory thymocytes by a process that is distinct from positive selection and deletion.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoantigens / genetics
  • CD4-Positive T-Lymphocytes / classification
  • CD4-Positive T-Lymphocytes / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Phenotype
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Interleukin-2 / metabolism*
  • Self Tolerance
  • Thymus Gland / cytology
  • Thymus Gland / immunology

Substances

  • Autoantigens
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2