Molecular mechanisms of CD4+ T-cell anergy

Nat Rev Immunol. 2007 Aug;7(8):599-609. doi: 10.1038/nri2131. Epub 2007 Jul 6.


Directing both innate and adaptive immune responses against foreign pathogens with correct timing, location and specificity is a fundamental objective for the immune system. Full activation of CD4+ T cells requires the binding of peptide-MHC complexes coupled with accessory signals provided by the antigen-presenting cell. However, aberrant activation of the T-cell receptor alone in mature T cells can produce a long-lived state of functional unresponsiveness, known as anergy. Recent studies probing both immune signalling pathways and the ubiquitin-proteasome system have helped to refine and elaborate current models for the molecular mechanisms underlying T-cell anergy. Controlling anergy induction and maintenance will be a key component in the future to mitigate unwanted T-cell activation that leads to autoimmune disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • Clonal Anergy / immunology*
  • Humans
  • Lymphocyte Activation / immunology
  • Proteome / immunology
  • Signal Transduction / immunology
  • Ubiquitin-Protein Ligases / immunology


  • Proteome
  • Ubiquitin-Protein Ligases