title: CD39/adenosine pathway is involved in AIDS progression.
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.
authors.affiliation: INSERM, Unite U955, Creteil, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Nikolova
authors.forename: Matthieu
authors.initials: M
authors.lastname: Carriere
authors.forename: Mohammad-Ali
authors.initials: MA
authors.lastname: Jenabian
authors.forename: Sophie
authors.initials: S
authors.lastname: Limou
authors.forename: Mehwish
authors.initials: M
authors.lastname: Younas
authors.forename: Ayrin
authors.initials: A
authors.lastname: Kök
authors.forename: Sophie
authors.initials: S
authors.lastname: Huë
authors.forename: Nabila
authors.initials: N
authors.lastname: Seddiki
authors.forename: Anne
authors.initials: A
authors.lastname: Hulin
authors.forename: Olivier
authors.initials: O
authors.lastname: Delaneau
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Herbeck
authors.forename: James I
authors.initials: JI
authors.lastname: Mullins
authors.forename: Maria
authors.initials: M
authors.lastname: Muhtarova
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Zagury
authors.forename: Jean-Daniel
authors.initials: JD
authors.lastname: Lelievre
authors.forename: Yves
authors.initials: Y
authors.lastname: Lévy
mesh_terms: D000241:Adenosine / Q000276:immunology* / Q000378:metabolism; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D001081:Apyrase / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002031:Bulgaria / Q000453:epidemiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D018450:Disease Progression; D015536:Down-Regulation; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D005602:France / Q000453:epidemiology; D015870:Gene Expression; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D008213:Lymphocyte Activation; D011110:Polymorphism, Genetic; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D043705:Receptor, Adenosine A2A; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine