CD39/Adenosine Pathway Is Involved in AIDS Progression

PLoS Pathogens

Hanneke Schuitemaker¹  Ayrin Kök²  Joshua T. Herbeck²  James I. Mullins³  Jean-Daniel Lelievre⁴  Mohammad-Ali Jenabian⁵  Nabila Seddiki⁵  Maria Nikolova⁵  Anne Hulin⁵  Yves Lévy⁵  Olivier Delaneau⁵  Mehwish Younas⁵  Sophie Limou⁵  Sophie Huë⁵  Matthieu Carriere⁶  Jean-François Zagury⁶  Armand Bensussan⁷  Maria Muhtarova⁷ 

[1] AP-HP, Groupe Henri-Mondor Albert-Chenevier, Laboratory of Pharmacology and Toxicology, Creteil, France;Chaire de Bioinformatique, Conservatoire National des Arts et Métiers, Paris, France;Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Center for Infectious Diseases and Immunity Amsterdam (CINIMA) Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;INSERM UMR 976 and Universite Denis-Diderot-Paris 7, Hopital Saint-Louis, Paris, France;INSERM, Unite U955, Creteil, France;National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria;University of Washington, School of Medicine, Department of Microbiology, Seattle, Washington, United States of America

关键词: Regulatory T cells;    T cells;    HIV-1;    Cytotoxic T cells;    Adenosine;    HIV infections;    HIV;    Immune activation;   

DOI  :  10.1371/journal.ppat.1002110

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

HIV-1 infection is characterized by a chronic activation of the immune system and suppressed function of T lymphocytes. Regulatory CD4+ CD25high FoxP3+CD127low 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.

【 授权许可】

CC BY