title: Regulatory T cells negatively affect IL-2 production of effector T cells through CD39/adenosine pathway in HIV infection.
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/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.
authors: Université Paris Est Créteil, Créteil, France.
authors: Mohammad-Ali
authors: MA
authors: Jenabian
authors: Nabila
authors: N
authors: Seddiki
authors: Ahmad
authors: A
authors: Yatim
authors: Matthieu
authors: M
authors: Carriere
authors: Anne
authors: A
authors: Hulin
authors: Mehwish
authors: M
authors: Younas
authors: Elnaz
authors: E
authors: Ghadimi
authors: Ayrin
authors: A
authors: Kök
authors: Jean-Pierre
authors: JP
authors: Routy
authors: Alain
authors: A
authors: Tremblay
authors: Jean
authors: J
authors: Sévigny
authors: Jean-Daniel
authors: JD
authors: Lelievre
authors: Yves
authors: Y
authors: Levy
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D001081:Apyrase / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism; D019175:DNA Methylation; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation; D011401:Promoter Regions, Genetic; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D007376:Interleukin-2; D043705:Receptor, Adenosine A2A; D000242:Cyclic AMP; D015720:5'-Nucleotidase; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine
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