Regulatory T cells negatively affect IL-2 production of effector T cells through CD39/adenosine pathway in HIV infection.
PLoS Pathog
; 9(4): e1003319, 2013.
Article
em En
| MEDLINE
| ID: mdl-23658513
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Apirase
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Antígenos CD
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Infecções por HIV
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Subpopulações de Linfócitos T
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Interleucina-2
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Linfócitos T Reguladores
Limite:
Humans
Idioma:
En
Revista:
PLoS Pathog
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
França