'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR

Nat Immunol. 2007 Oct;8(10):1049-59. doi: 10.1038/ni1512. Epub 2007 Sep 16.


T cell immunity requires the long-term survival of T cells that are capable of recognizing self antigens but are not overtly autoreactive. How this balance is achieved remains incompletely understood. Here we identify a homeostatic mechanism that transcriptionally tailors CD8 coreceptor expression in individual CD8+ T cells to the self-specificity of their clonotypic T cell receptor (TCR). 'Coreceptor tuning' results from interplay between cytokine and TCR signals, such that signals from interleukin 7 and other common gamma-chain cytokines transcriptionally increase CD8 expression and thereby promote TCR engagement of self ligands, whereas TCR signals impair common gamma-chain cytokine signaling and thereby decrease CD8 expression. This dynamic interplay induces individual CD8+ T cells to express CD8 in quantities appropriate for the self-specificity of their TCR, promoting the engagement of self ligands, yet avoiding autoreactivity.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • CD8 Antigens / genetics*
  • CD8-Positive T-Lymphocytes / physiology
  • Cells, Cultured
  • Cytokines / pharmacology
  • Enhancer Elements, Genetic
  • Homeostasis
  • Humans
  • Interleukin-7 / pharmacology*
  • Mice
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction / physiology*
  • Transcription, Genetic*
  • Up-Regulation


  • CD8 Antigens
  • Cytokines
  • Interleukin-7
  • Receptors, Antigen, T-Cell