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Prepublished online as a Blood First Edition Paper on November 21, 2002; DOI 10.1182/blood-2002-07-2113.

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Submitted July 17, 2002
Accepted October 15, 2002

Adenosine affects expression of membrane molecules, cytokine, and chemokine release, and the T cell stimulatory capacity of human dendritic cells

Elisabeth Panther, Silvia Corinti, Marco Idzko, Yared Herouy, Matthias Napp, Andrea la Sala, Giampiero Girolomoni, and Johannes Norgauer*

Department of Experimental Dermatology, University of Freiburg, Freiburg, Germany
Department of Pneumology, University of Freiburg, Freiburg, Germany
Istituto Dermopatico dell`Immacolata, Laboratory of Immunology, Rome, Italy

* Corresponding author; email: norgauer{at}haut.ukl.uni-freiburg.de.

Dendritic cells (DC) express functional purinergic type 1 receptors, but the effects of adenosine in these antigen presenting cells have been only marginally investigated. Here, we further characterized the biological activity of adenosine in immature DC (iDC) and lipopolysaccharide (LPS)-matured DC (mDC). Chronic stimulation with adenosine enhanced the macropinocytotic activity and the membrane expression of CD80, CD86, MHC class I and HLA-DR molecules on iDC. Adenosine also increased LPS-induced CD54, CD80, MHC class I and HLA-DR molecule expression in mDC. In addition, adenosine dose-dependently inhibited tumor necrosis factor {alpha} and interleukin (IL)-12 release, whereas enhanced the secretion of IL-10 from mDC. The use of selective receptor agonists revealed that the modulation of the cytokine and cell surface marker profile was due to activation of A2 adenosine receptor. Functionally, adenosine reduced the allostimmulatory capacity of iDC, but not of mDC. More important, DC matured in the presence of adenosine had a reduced capacity to induce Th1 polarization of naive CD4+ T lymphocytes. Finally, adenosine augmented the release of the chemokine CCL17 and inhibited CXCL10 production by mDC. In aggregate, the results provide initial evidence that adenosine diminishes the capacity of DC to initiate and amplify Th1 immune responses.


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