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

• Published in: Blood Vol. 101; no. 10; pp. 3985 - 3990
• Main Authors: Panther, Elisabeth, Corinti, Silvia, Idzko, Marco, Herouy, Yared, Napp, Matthias, la Sala, Andrea, Girolomoni, Giampiero, Norgauer, Johannes
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15-05-2003; The Americain Society of Hematology
• Subjects: Adenosine - analogs & derivatives; Adenosine - pharmacology; Analysis of the immune response. Humoral and cellular immunity; Antigens, CD - blood; Biological and medical sciences; Cells, Cultured; Chemokines - blood; Cytokines - blood; Dendritic Cells - drug effects; Dendritic Cells - immunology; Endocytosis - drug effects; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Histocompatibility Antigens Class I - blood; Humans; Immunobiology; Interleukin-12 - blood; Kinetics; Lipopolysaccharides - pharmacology; Lymphocyte Activation; Organs and cells involved in the immune response; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tumor Necrosis Factor-alpha - metabolism; Chemokine; Human; Dendritic cell; Adenosine; Purine nucleoside; Immune response; Antigen presenting cell; Cytokine; T-Lymphocyte; Plasma membrane; Th1 lymphocyte; Cellular immunity
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-07-2113

Dendritic cells (DCs) 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 biologic activity of adenosine in immature DCs (iDCs) and lipopolysaccharide (LPS)–matured DCs (mDCs). Chronic stimulation with adenosine enhanced the macropinocytotic activity and the membrane expression of CD80, CD86, major histocompatibility complex (MHC) class I, and HLA-DR molecules on iDCs. Adenosine also increased LPS-induced CD54, CD80, MHC class I, and HLA-DR molecule expression in mDCs. In addition, adenosine dose-dependently inhibited tumor necrosis factor α and interleukin-12 (IL-12) release, whereas it enhanced the secretion of IL-10 from mDCs. 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 allostimulatory capacity of iDCs, but not of mDCs. More important, DCs matured in the presence of adenosine had a reduced capacity to induce T helper 1 (Th1) polarization of naive CD4+ T lymphocytes. Finally, adenosine augmented the release of the chemokine CCL17 and inhibited CXCL10 production by mDCs. In aggregate, the results provide initial evidence that adenosine diminishes the capacity of DCs to initiate and amplify Th1 immune responses.