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

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.