T regulatory cells: hypoxia-adenosinergic suppression and re-direction of the immune response

Trends Immunol. 2009 Mar;30(3):102-8. doi: 10.1016/j.it.2008.12.002. Epub 2009 Feb 7.


T regulatory cells (Treg cells) suppress immune responses to maintain self tolerance, but they also protect cancerous tissues. I propose a model to potentially unify the diverse functions of Treg cells. This assumes that Treg cells provide a complementary immunological arm to a physiological tissue-protecting mechanism, driven by low oxygen tension (i.e. hypoxia) in inflamed or cancerous tissues. The cAMP-elevating A2A and A2B adenosine receptors, hypoxia inducible transcription factor 1alpha (HIF), the cAMP response element (CRE)- and hypoxia response element (HRE)-mediated transcription in Treg and effector cells have key roles in this model. Both the T cell receptor (TCR)-triggered- and HRE- and CRE-driven activities of Treg cells are required to achieve a maximal level of immune suppression.

Publication types

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

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / metabolism*
  • Animals
  • Cell Hypoxia / immunology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / immunology
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Receptor, Adenosine A2A / immunology
  • Receptor, Adenosine A2A / metabolism*
  • Receptor, Adenosine A2B / immunology
  • Receptor, Adenosine A2B / metabolism*
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism


  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Receptor, Adenosine A2A
  • Receptor, Adenosine A2B
  • Adenosine