Nikolova M, Carriere M, Jenabian MA, Limou S, Younas M, Kök A, Huë S, Seddiki N, Hulin A, Delaneau O, Schuitemaker H, Herbeck JT, Mullins JI, Muhtarova M, Bensussan A, Zagury JF, Lelievre JD, Lévy Y (2011). CD39/adenosine pathway is involved in AIDS progression. PLoS pathogens, 7(7), e1002110. (pubmed) (doi)
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.