Regulatory T Cells Negatively Affect IL-2 Production of Effector T Cells through CD39/Adenosine Pathway in HIV Infection

The mechanisms by which regulatory t cells suppress il-2 production of effector cd4+ t cells in pathological conditions are unclear. a subpopulation of human treg expresses the ectoenzyme cd39,which in association with cd73 converts atp/adp/amp to adenosine. we show here that treg/cd39+ suppress il-2 expression of activated cd4+ t-cells more efficiently than treg/cd39-. this inhibition is due to the demethylation of an essential cpg site of the il-2 gene promoter,which was reversed by an anti-cd39 mab. by recapitulating the events downstream cd39/adenosine receptor (a2ar) axis,we show that a2ar agonist and soluble camp inhibit cpg site demethylation of the il-2 gene promoter. a high frequency of treg/cd39+ is associated with a low clinical outcome in hiv infection. we show here that cd4+ t-cells from hiv-1 infected individuals express high levels of a2ar and intracellular camp. following in vitro stimulation,these cells exhibit a lower degree of demethylation of il-2 gene promoter associated with a lower expression of il-2,compared to healthy individuals. these results extend previous data on the role of treg in hiv infection by filling the gap between expansion of treg/cd39+ in hiv infection and the suppression of cd4+ t-cell function through inhibition of il-2 production. © 2013 jenabian et al.