CD39/adenosine pathway is involved in AIDS progression.
| Autor: | Maria Nikolova, Matthieu Carriere, Mohammad-Ali Jenabian, Sophie Limou, Mehwish Younas, Ayrin Kök, Sophie Huë, Nabila Seddiki, Anne Hulin, Olivier Delaneau, Hanneke Schuitemaker, Joshua T Herbeck, James I Mullins, Maria Muhtarova, Armand Bensussan, Jean-François Zagury, Jean-Daniel Lelievre, Yves Lévy |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | PLoS Pathogens, Vol 7, Iss 7, p e1002110 (2011) |
| Druh dokumentu: | article |
| ISSN: | 1553-7366 1553-7374 |
| DOI: | 10.1371/journal.ppat.1002110 |
| Popis: | 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. |
| Databáze: | Directory of Open Access Journals |
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