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

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

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New England Inflammation and Tissue Protection Institute, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.


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.

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