SEARCH:   Advanced

Blood, 15 April 2007, Vol. 109, No. 8, pp. 3351-3359. Prepublished online as a Blood First Edition Paper on December 7, 2006; DOI 10.1182/blood-2006-07-034785. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-07-034785v1 109/8/3351    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 Boasso, A. Articles by Shearer, G. M. Search for Related Content PubMed PubMed Citation Articles by Boasso, A. Articles by Shearer, G. M. Related Collections Related Articles in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells Adriano Boasso1, Jean-Philippe Herbeuval1,2, Andrew W. Hardy1, Stephanie A. Anderson3, Matthew J. Dolan4, Dietmar Fuchs5, and Gene M. Shearer1 1 Experimental Immunology Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD; 2 Unite Mixte de Recherche, Centre National de la Recherche Scientifique 8147, Hopital Necker, Université Paris V, Paris, France; 3 Henry M. Jackson Foundation and Infectious Diseases Service, Wilford Hall Medical Center, Lackland Air Force Base, TX; 4 Defense Institute for Medical Operations, Brooks City-Base, and Infectious Diseases Service, Wilford Hall Medical Center, Lackland Air Force Base, TX; 5 Division of Biological Chemistry, Biocentre, Innsbruck Medical University and Ludwig Boltzmann Institute of AIDS-Research, Innsbruck, Austria Infection with the human immunodeficiency virus type-1 (HIV) results in acute and progressive numeric loss of CD4+ T-helper cells and functional impairment of T-cell responses. The mechanistic basis of the functional impairment of the surviving cells is not clear. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme that inhibits T-cell proliferation by catabolizing the essential amino acid tryptophan (Trp) into the kynurenine (kyn) pathway. Here, we show that IDO mRNA expression is elevated in peripheral blood mononuclear cells (PBMCs) from HIV+ patients compared with uninfected healthy controls (HCs), and that in vitro inhibition of IDO with the competitive blocker 1-methyl tryptophan (1-mT) results in increased CD4+ T-cell proliferative response in PBMCs from HIV-infected patients. We developed an in vitro model in which exposure of PBMCs from HCs to either infectious or noninfectious, R5- or X4-tropic HIV induced IDO in plasmacytoid dendritic cells (pDCs). HIV-induced IDO was not inhibited by blocking antibodies against interferon type I or type II, which, however, induced IDO in pDCs when added to PBMC cultures. Blockade of gp120/CD4 interactions with anti-CD4 Ab inhibited HIV-mediated IDO induction. Thus, induction of IDO in pDCs by HIV may contribute to the T-cell functional impairment observed in HIV/AIDS by a non–interferon-dependent mechanism. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Articles in Blood Online: CTLA-4 blockade decreases TGF-, IDO, and viral RNA expression in tissues of SIVmac251-infected macaques Anna Hryniewicz, Adriano Boasso, Yvette Edghill-Smith, Monica Vaccari, Dietmar Fuchs, David Venzon, Janos Nacsa, Michael R. Betts, Wen-Po Tsai, Jean-Michel Heraud, Brigitte Beer, Diann Blanset, Claire Chougnet, Israel Lowy, Gene M. Shearer, and Genoveffa Franchini Blood 2006 108: 3834-3842. [Abstract] [Full Text] [PDF] HIV-1–driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS Jakob Nilsson, Adriano Boasso, Paula Andrea Velilla, Rui Zhang, Monica Vaccari, Genoveffa Franchini, Gene M. Shearer, Jan Andersson, and Claire Chougnet Blood 2006 108: 3808-3817. [Abstract] [Full Text] [PDF] This article has been cited by other articles: F. Pascale, V. Contreras, M. Bonneau, A. Courbet, S. Chilmonczyk, C. Bevilacqua, M. Eparaud, V. Niborski, S. Riffault, A.-M. Balazuc, et al. Plasmacytoid Dendritic Cells Migrate in Afferent Skin Lymph J. Immunol., May 1, 2008; 180(9): 5963 - 5972. [Abstract] [Full Text] [PDF] V. Cecchinato, E. Tryniszewska, Z. M. Ma, M. Vaccari, A. Boasso, W.-P. Tsai, C. Petrovas, D. Fuchs, J.-M. Heraud, D. Venzon, et al. Immune Activation Driven by CTLA-4 Blockade Augments Viral Replication at Mucosal Sites in Simian Immunodeficiency Virus Infection J. Immunol., April 15, 2008; 180(8): 5439 - 5447. [Abstract] [Full Text] [PDF] S. Li, E. J. Gowans, C. Chougnet, M. Plebanski, and U. Dittmer Natural Regulatory T Cells and Persistent Viral Infection J. Virol., January 1, 2008; 82(1): 21 - 30. [Full Text] [PDF] V. Saxena, J. K. Ondr, A. F. Magnusen, D. H. Munn, and J. D. Katz The Countervailing Actions of Myeloid and Plasmacytoid Dendritic Cells Control Autoimmune Diabetes in the Nonobese Diabetic Mouse J. Immunol., October 15, 2007; 179(8): 5041 - 5053. [Abstract] [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020