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Blood, 15 June 2005, Vol. 105, No. 12, pp. 4707-4714. Prepublished online as a Blood First Edition Paper on March 3, 2005; DOI 10.1182/blood-2004-04-1407. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-04-1407v1 105/12/4707    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Erdmann, A. A. Articles by Fowler, D. H. Search for Related Content PubMed PubMed Citation Articles by Erdmann, A. A. Articles by Fowler, D. H. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Activation of Th1 and Tc1 cell adenosine A2A receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo Andreas A. Erdmann, Zhan-Guo Gao, Unsu Jung, Jason Foley, Todd Borenstein, Kenneth A. Jacobson, and Daniel H. Fowler From the Experimental Transplantation and Immunology Branch, National Cancer Institute, the Molecular Recognition Section, Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD. To evaluate the direct effect of adenosine on cytokine-polarized effector T cells, murine type 1 helper T cells (Th1) and type 1 cytotoxic T lymphocytes (Tc1) and Th2/Tc2 cells were generated using an antigen-presenting cell (APC)-free method. Tc1 and Tc2 cells had similar adenosine signaling, as measured by intracellular cyclic AMP (cAMP) increase upon adenosine A2A receptor agonism by CGS21680(CGS). CGS greatly reduced Tc1 and Tc2 cell interleukin 2 (IL-2) and tumor necrosis factor (TNF-) secretion, with nominal effect on interferon (IFN-) secretion. Tc2 cell IL-4 and IL-5 secretion was not reduced by CGS, and IL-10 secretion was moderately reduced. Agonist-mediated inhibition of IL-2 and TNF- secretion occurred via A2A receptors, with no involvement of A1, A2B, or A3 receptors. Adenosine agonist concentrations that abrogated cytokine secretion did not inhibit Tc1 or Tc2 cell cytolytic function. Adenosine modulated effector T cells in vivo, as CGS administration reduced CD4+Th1 and CD8+Tc1 cell expansion to alloantigen and, in a separate model, reduced antigen-specific CD4+ Th1 cell numbers. Remarkably, agonist-mediated T-cell inhibition was abrogated by in vivo IL-2 therapy. Adenosine receptor activation therefore preferentially inhibits type I cytokine secretion, most notably IL-2. Modulation of adenosine receptors may thus represent a suitable target primarily for inflammatory conditions mediated by Th1 and Tc1 cells. (Blood. 2005;105: 4707-4714) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Huang, Z. Lei, G.-M. Zhang, D. Li, C. Song, B. Li, Y. Liu, Y. Yuan, J. Unkeless, H. Xiong, et al. SCF-mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment Blood, August 15, 2008; 112(4): 1269 - 1279. [Abstract] [Full Text] [PDF] P. E. Zarek, C.-T. Huang, E. R. Lutz, J. Kowalski, M. R. Horton, J. Linden, C. G. Drake, and J. D. Powell A2A receptor signaling promotes peripheral tolerance by inducing T-cell anergy and the generation of adaptive regulatory T cells Blood, January 1, 2008; 111(1): 251 - 259. [Abstract] [Full Text] [PDF] T. Raskovalova, A. Lokshin, X. Huang, Y. Su, M. Mandic, H. M. Zarour, E. K. Jackson, and E. Gorelik Inhibition of Cytokine Production and Cytotoxic Activity of Human Antimelanoma Specific CD8+ and CD4+ T Lymphocytes by Adenosine-Protein Kinase A Type I Signaling Cancer Res., June 15, 2007; 67(12): 5949 - 5956. [Abstract] [Full Text] [PDF] T. Bopp, C. Becker, M. Klein, S. Klein-Hessling, A. Palmetshofer, E. Serfling, V. Heib, M. Becker, J. Kubach, S. Schmitt, et al. Cyclic adenosine monophosphate is a key component of regulatory T cell mediated suppression J. Exp. Med., June 11, 2007; 204(6): 1303 - 1310. [Abstract] [Full Text] [PDF] S. Deaglio, K. M. Dwyer, W. Gao, D. Friedman, A. Usheva, A. Erat, J.-F. Chen, K. Enjyoji, J. Linden, M. Oukka, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression J. Exp. Med., June 11, 2007; 204(6): 1257 - 1265. [Abstract] [Full Text] [PDF] J. J. Kobie, P. R. Shah, L. Yang, J. A. Rebhahn, D. J. Fowell, and T. R. Mosmann T Regulatory and Primed Uncommitted CD4 T Cells Express CD73, Which Suppresses Effector CD4 T Cells by Converting 5'-Adenosine Monophosphate to Adenosine J. Immunol., November 15, 2006; 177(10): 6780 - 6786. [Abstract] [Full Text] [PDF] E. J. Carrier, J. A. Auchampach, and C. J. Hillard Inhibition of an equilibrative nucleoside transporter by cannabidiol: A mechanism of cannabinoid immunosuppression PNAS, May 16, 2006; 103(20): 7895 - 7900. [Abstract] [Full Text] [PDF]

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