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

Molecular mechanisms of CD4+ T-cell anergy.

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Stanford University School of Medicine, Department of Medicine, Division of Immunology and Rheumatology, CCSR Building, 269 Campus Drive, Room 2225, Stanford, California 94305-5166, USA.


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.

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