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PLoS Pathog. 2011 Jul;7(7):e1002110. doi: 10.1371/journal.ppat.1002110. Epub 2011 Jul 7.

CD39/adenosine pathway is involved in AIDS progression.

Author information

1
INSERM, Unite U955, Creteil, France.

Abstract

HIV-1 infection is characterized by a chronic activation of the immune system and suppressed function of T lymphocytes. Regulatory CD4+ CD25(high) FoxP3+CD127(low) T cells (Treg) play a key role in both conditions. Here, we show that HIV-1 positive patients have a significant increase of Treg-associated expression of CD39/ENTPD1, an ectoenzyme which in concert with CD73 generates adenosine. We show in vitro that the CD39/adenosine axis is involved in Treg suppression in HIV infection. Treg inhibitory effects are relieved by CD39 down modulation and are reproduced by an adenosine-agonist in accordance with a higher expression of the adenosine A2A receptor on patients' T cells. Notably, the expansion of the Treg CD39+ correlates with the level of immune activation and lower CD4+ counts in HIV-1 infected patients. Finally, in a genetic association study performed in three different cohorts, we identified a CD39 gene polymorphism that was associated with down-modulated CD39 expression and a slower progression to AIDS.

PMID:
21750674
PMCID:
PMC3131268
DOI:
10.1371/journal.ppat.1002110
[Indexed for MEDLINE]
Free PMC Article

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