SEARCH:   Advanced

Blood, 15 August 2007, Vol. 110, No. 4, pp. 1225-1232. Prepublished online as a Blood First Edition Paper on April 20, 2007; DOI 10.1182/blood-2006-12-064527. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-12-064527v1 110/4/1225    most recent Alert me when this article is cited Alert me if a correction is posted 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 Borsellino, G. Articles by Falk, K. Search for Related Content PubMed PubMed Citation Articles by Borsellino, G. Articles by Falk, K. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 21, 2006 Accepted April 16, 2007 Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression Giovanna Borsellino, Markus Kleinewietfeld, Diletta Di Mitri, Alexander Sternjak, Adamo Diamantini, Raffaella Giometto, Sabine Hopner, Diego Centonze, Giorgio Bernardi, Maria Luisa Dell'Acqua, Paolo Maria Rossini, Luca Battistini, Olaf Rotzschke, and Kirsten Falk* Laboratory of Neuroimmunology, Fondazione Santa Lucia, Rome, Italy Cellular Immunology of Autoimmune Reactions, Max-Delbruck-Center for Molecular Medicine, Berlin, Germany Neurology Unit, Universita' di Roma Tor Vergata, Rome, Italy Neurology Unit, University of Rome Campus Biomedico, Rome, Italy * Corresponding author; email: falk{at}mdc-berlin.de. In the immune system extracellular ATP functions as a 'natural adjuvant' that exhibits multiple proinflammatory effects. It is released by damaged cells as an indicator of trauma and cell death but can be inactivated by CD39 (nucleoside triphosphate diphosphohydrolase-1, NTPDase 1), an ectoenzyme that degrades ATP to AMP. Here we show that CD39 is expressed primarily by immune-suppressive Foxp3+ regulatory T cells (Treg). In mice, the enzyme is present on virtually all CD4+CD25+ cells. CD39 expression is driven by the Treg-specific transcription factor Foxp3 and its catalytic activity is strongly enhanced by TCR-ligation. Activated Treg cells are therefore able to abrogate ATP-related effects such as P2 receptor-mediated cell toxicity and ATP-driven maturation of dendritic cells. Also human Treg cells express CD39. In contrast to mice, CD39-expression in man is restricted to a subset of Foxp3+ regulatory effector/memory-like T cells (TREM). Notably, patients suffering of the remitting/relapsing form of multiple sclerosis (MS) have strikingly reduced numbers of CD39+ Treg cells in the blood. Thus, in humans CD39 is a marker of a Treg subset likely involved in the control of the inflammatory autoimmune disease. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: Hydrolysis of extracellular ATP and immune suppression: humans versus mice Stefania Gorini and Andrea la Sala Blood 2008 111: 964-965. [Full Text] [PDF] Hydrolysis of extracellular ATP by CD39+ Treg cells: context matters! Markus Kleinewietfeld, Diletta DiMitri, Alexander Sternjak, Adamo Diamantini, Giovanna Borsellino, Luca Battistini, Olaf Rötzschke, and Kirsten Falk Blood 2008 111: 965-966. [Full Text] [PDF] This article has been cited by other articles: J. M. Fletcher, R. Lonergan, L. Costelloe, K. Kinsella, B. Moran, C. O'Farrelly, N. Tubridy, and K. H. G. Mills CD39+Foxp3+ Regulatory T Cells Suppress Pathogenic Th17 Cells and Are Impaired in Multiple Sclerosis J. Immunol., December 1, 2009; 183(11): 7602 - 7610. [Abstract] [Full Text] [PDF] M. Mandapathil, M. J. Szczepanski, M. Szajnik, J. Ren, D. E. Lenzner, E. K. Jackson, E. Gorelik, S. Lang, J. T. Johnson, and T. L. Whiteside Increased Ectonucleotidase Expression and Activity in Regulatory T Cells of Patients with Head and Neck Cancer Clin. Cancer Res., October 15, 2009; 15(20): 6348 - 6357. [Abstract] [Full Text] [PDF] C. Becker, C. Taube, T. Bopp, C. Becker, K. Michel, J. Kubach, S. Reuter, N. Dehzad, M. F. Neurath, K. Reifenberg, et al. Protection from graft-versus-host disease by HIV-1 envelope protein gp120-mediated activation of human CD4+CD25+ regulatory T cells Blood, August 6, 2009; 114(6): 1263 - 1269. [Abstract] [Full Text] [PDF] I. Kryczek, M. Banerjee, P. Cheng, L. Vatan, W. Szeliga, S. Wei, E. Huang, E. Finlayson, D. Simeone, T. H. Welling, et al. Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments Blood, August 6, 2009; 114(6): 1141 - 1149. [Abstract] [Full Text] [PDF] G. R. Kinsey, R. Sharma, L. Huang, L. Li, A. L. Vergis, H. Ye, S.-T. Ju, and M. D. Okusa Regulatory T Cells Suppress Innate Immunity in Kidney Ischemia-Reperfusion Injury J. Am. Soc. Nephrol., August 1, 2009; 20(8): 1744 - 1753. [Abstract] [Full Text] [PDF] L.-F. Lu and A. Rudensky Molecular orchestration of differentiation and function of regulatory T cells Genes & Dev., June 1, 2009; 23(11): 1270 - 1282. [Abstract] [Full Text] [PDF] M. J. Szczepanski, M. Szajnik, M. Czystowska, M. Mandapathil, L. Strauss, A. Welsh, K. A. Foon, T. L. Whiteside, and M. Boyiadzis Increased Frequency and Suppression by Regulatory T Cells in Patients with Acute Myelogenous Leukemia Clin. Cancer Res., May 15, 2009; 15(10): 3325 - 3332. [Abstract] [Full Text] [PDF] S. Andre, D. F. Tough, S. Lacroix-Desmazes, S. V. Kaveri, and J. Bayry Surveillance of Antigen-Presenting Cells by CD4+CD25+ Regulatory T Cells in Autoimmunity: Immunopathogenesis and Therapeutic Implications Am. J. Pathol., May 1, 2009; 174(5): 1575 - 1587. [Abstract] [Full Text] [PDF] J. M. Wilson, W. G. Ross, O. N. Agbai, R. Frazier, R. A. Figler, J. Rieger, J. Linden, and P. B. Ernst The A2B Adenosine Receptor Impairs the Maturation and Immunogenicity of Dendritic Cells J. Immunol., April 15, 2009; 182(8): 4616 - 4623. [Abstract] [Full Text] [PDF] O. Rotzschke, G. Borsellino, L. Battistini, K. Falk, and M. Kleinewietfeld In vivo-activated CD103+ Foxp3+ Tregs: of men and mice Blood, February 26, 2009; 113(9): 2119 - 2120. [Full Text] [PDF] D. Zeng, D. Zhao, and R. Nakamura Response: Is CD103 a good surface marker for in vivo-activated effector/memory Treg cells in patients with chronic inflammation? Unknown yet Blood, February 26, 2009; 113(9): 2120 - 2120. [Full Text] [PDF] L. Strauss, C. Bergmann, and T. L. Whiteside Human Circulating CD4+CD25highFoxp3+ Regulatory T Cells Kill Autologous CD8+ but Not CD4+ Responder Cells by Fas-Mediated Apoptosis J. Immunol., February 1, 2009; 182(3): 1469 - 1480. [Abstract] [Full Text] [PDF] F. M. Sansom, S. C. Robson, and E. L. Hartland Possible Effects of Microbial Ecto-Nucleoside Triphosphate Diphosphohydrolases on Host-Pathogen Interactions Microbiol. Mol. Biol. Rev., December 1, 2008; 72(4): 765 - 781. [Abstract] [Full Text] [PDF] M. Saresella, I. Marventano, R. Longhi, F. Lissoni, D. Trabattoni, L. Mendozzi, D. Caputo, and M. Clerici CD4+CD25+FoxP3+PD1- regulatory T cells in acute and stable relapsing-remitting multiple sclerosis and their modulation by therapy FASEB J, October 1, 2008; 22(10): 3500 - 3508. [Abstract] [Full Text] [PDF] U. Schenk, A. M. Westendorf, E. Radaelli, A. Casati, M. Ferro, M. Fumagalli, C. Verderio, J. Buer, E. Scanziani, and F. Grassi Purinergic Control of T Cell Activation by ATP Released Through Pannexin-1 Hemichannels Sci. Signal., September 30, 2008; 1(39): ra6 - ra6. [Abstract] [Full Text] [PDF] I. Kochetkova, T. Trunkle, G. Callis, and D. W. Pascual Vaccination without Autoantigen Protects against Collagen II-Induced Arthritis via Immune Deviation and Regulatory T Cells J. Immunol., August 15, 2008; 181(4): 2741 - 2752. [Abstract] [Full Text] [PDF] J. H. Mills, L. F. Thompson, C. Mueller, A. T. Waickman, S. Jalkanen, J. Niemela, L. Airas, and M. S. Bynoe CD73 is required for efficient entry of lymphocytes into the central nervous system during experimental autoimmune encephalomyelitis PNAS, July 8, 2008; 105(27): 9325 - 9330. [Abstract] [Full Text] [PDF] F. M. Sansom, P. Riedmaier, H. J. Newton, M. A. Dunstone, C. E. Muller, H. Stephan, E. Byres, T. Beddoe, J. Rossjohn, P. J. Cowan, et al. Enzymatic Properties of an Ecto-nucleoside Triphosphate Diphosphohydrolase from Legionella pneumophila: SUBSTRATE SPECIFICITY AND REQUIREMENT FOR VIRULENCE J. Biol. Chem., May 9, 2008; 283(19): 12909 - 12918. [Abstract] [Full Text] [PDF] M. Kleinewietfeld, D. DiMitri, A. Sternjak, A. Diamantini, G. Borsellino, L. Battistini, O. Rotzschke, and K. Falk Hydrolysis of extracellular ATP by CD39+ Treg cells: context matters! Blood, January 15, 2008; 111(2): 965 - 966. [Full Text] [PDF] S. Gorini and A. la Sala Hydrolysis of extracellular ATP and immune suppression: humans versus mice Blood, January 15, 2008; 111(2): 964 - 965. [Full Text] [PDF]

	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020