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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2480-2486. Prepublished online as a Blood First Edition Paper on November 30, 2004; DOI 10.1182/blood-2004-06-2103. This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 2004-06-2103v1 105/6/2480    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 Terness, P. Articles by Opelz, G. Search for Related Content PubMed PubMed Citation Articles by Terness, P. Articles by Opelz, G. Related Collections Immunobiology Phagocytes Gene Expression Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Regulation of human auto- and alloreactive T cells by indoleamine 2,3-dioxygenase (IDO)–producing dendritic cells: too much ado about IDO? Peter Terness, Jing-Jing Chuang, Thomas Bauer, Lucian Jiga, and Gerhard Opelz From the Institute of Immunology, Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany. Although dendritic cells (DCs) strongly stimulate the immune response, they can also induce unresponsiveness. Recently, a human monocyte-derived DC subpopulation was described that constitutively expresses indoleamine 2,3-dioxygenase (IDO). These DCs were defined as nonadherent CD123+/CC chemokine receptor 6+ (CCR6+) cells that suppress the allogeneic T-cell response. In the present study, we generated nonadherent, mature DCs from human blood monocytes. As expected, in addition to the classic markers, these cells expressed CD123 and CCR6. Reverse transcription–polymerase chain reaction (RT-PCR), however, did not show IDO gene transcription, nor did we detect enzymatic IDO activity. Treating the cells with interferon- (IFN-) resulted in significant IDO production. Subsequently, we studied the regulatory properties of IDO-producing DCs on autologous and allogeneic T-cell responses. Neither OKT3-stimulated T cells of healthy donors nor myelin basic protein (MBP)–specific T cells of patients with multiple sclerosis (MS) were suppressed by autologous IDO DCs. However, whereas IDOneg DCs supported further stimulation of preactivated MBP-specific T cells of an MS patient, IDOpos DCs had lost this capacity. The allogeneic T-cell response was only marginally suppressed by IDO DCs. Our findings show that nonadherent CD123+/CCR6+ human DCs do not constitutively express IDO, and, even if they express the enzyme after IFN- treatment, they possess only limited T-cell regulatory function. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letter in Blood Online: Dendritic cells have the option to express IDO-mediated suppression or not David H. Munn, Andrew L. Mellor, Marco Rossi, and James W. Young Blood 2005 105: 2618. [Full Text] [PDF] This article has been cited by other articles: B. Jurgens, U. Hainz, D. Fuchs, T. Felzmann, and A. Heitger Interferon-{gamma}-triggered indoleamine 2,3-dioxygenase competence in human monocyte-derived dendritic cells induces regulatory activity in allogeneic T cells Blood, October 8, 2009; 114(15): 3235 - 3243. [Abstract] [Full Text] [PDF] F. Qian, J. Villella, P. K. Wallace, P. Mhawech-Fauceglia, J. D. Tario Jr., C. Andrews, J. Matsuzaki, D. Valmori, M. Ayyoub, P. J. Frederick, et al. Efficacy of Levo-1-Methyl Tryptophan and Dextro-1-Methyl Tryptophan in Reversing Indoleamine-2,3-Dioxygenase-Mediated Arrest of T-Cell Proliferation in Human Epithelial Ovarian Cancer Cancer Res., July 1, 2009; 69(13): 5498 - 5504. [Abstract] [Full Text] [PDF] A. Curti, S. Trabanelli, V. Salvestrini, M. Baccarani, and R. M. Lemoli The role of indoleamine 2,3-dioxygenase in the induction of immune tolerance: focus on hematology Blood, March 12, 2009; 113(11): 2394 - 2401. [Abstract] [Full Text] [PDF] S. Rutella, S. Danese, and G. Leone Tolerogenic dendritic cells: cytokine modulation comes of age Blood, September 1, 2006; 108(5): 1435 - 1440. [Abstract] [Full Text] [PDF] S. Agaugue, L. Perrin-Cocon, F. Coutant, P. Andre, and V. Lotteau 1-Methyl-Tryptophan Can Interfere with TLR Signaling in Dendritic Cells Independently of IDO Activity J. Immunol., August 15, 2006; 177(4): 2061 - 2071. [Abstract] [Full Text] [PDF] C. Orabona, P. Puccetti, C. Vacca, S. Bicciato, A. Luchini, F. Fallarino, R. Bianchi, E. Velardi, K. Perruccio, A. Velardi, et al. Toward the identification of a tolerogenic signature in IDO-competent dendritic cells Blood, April 1, 2006; 107(7): 2846 - 2854. [Abstract] [Full Text] [PDF] T. Luft, E. Maraskovsky, and M. Schnurr IDO production, adaptive immunity, and CTL killing Blood, October 1, 2005; 106(7): 2228 - 2229. [Full Text] [PDF] D. Braun, R. S. Longman, and M. L. Albert A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation Blood, October 1, 2005; 106(7): 2375 - 2381. [Abstract] [Full Text] [PDF] D. H. Munn, A. L. Mellor, M. Rossi, and J. W. Young Dendritic cells have the option to express IDO-mediated suppression or not Blood, March 15, 2005; 105(6): 2618 - 2618. [Full Text] [PDF]

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