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- Title
Regulatory T Cells Negatively Affect IL-2 Production of Effector T Cells through CD39/Adenosine Pathway in HIV Infection.
- Authors
Jenabian, Mohammad-Ali; Seddiki, Nabila; Yatim, Ahmad; Carriere, Matthieu; Hulin, Anne; Younas, Mehwish; Ghadimi, Elnaz; Kök, Ayrin; Routy, Jean-Pierre; Tremblay, Alain; Sévigny, Jean; Lelievre, Jean-Daniel; Levy, Yves
- Abstract
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/CD392-. 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.
- Subjects
T cells; LYMPHOCYTES; INTERLEUKIN-2; IMMUNOMODULATORS; ADENOSINES
- Publication
PLoS Pathogens, 2013, Vol 9, Issue 4, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1003319