CD39/adenosine Pathway Is Involved in AIDS Progression

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

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.

MeSH terms

  • Adenosine / immunology*
  • Adenosine / metabolism
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Apyrase / immunology*
  • Apyrase / metabolism
  • Biomarkers / metabolism
  • Bulgaria / epidemiology
  • Cell Proliferation
  • Cells, Cultured
  • Disease Progression
  • Down-Regulation
  • Forkhead Transcription Factors / immunology
  • Forkhead Transcription Factors / metabolism
  • France / epidemiology
  • Gene Expression
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • HIV Infections / mortality
  • Humans
  • Lymphocyte Activation
  • Polymorphism, Genetic
  • Receptor, Adenosine A2A / genetics
  • Receptor, Adenosine A2A / metabolism
  • Survival Rate
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Antigens, CD
  • Biomarkers
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Receptor, Adenosine A2A
  • Apyrase
  • CD39 antigen
  • Adenosine