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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 (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 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 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  |  Next Article  Submitted July 18, 2006 Accepted December 1, 2006 HIV-1 inhibits CD4+ T cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells Adriano Boasso*, Jean-Philippe Herbeuval, Andrew W Hardy, Stephanie A Anderson, Matthew J Dolan, Dietmar Fuchs, and Gene M Shearer Experimental Immunology Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD Hopital Necker, Universite Paris V, Paris, France Henry M. Jackson Foundation and Infectious Diseases Service, Wilford Hall Medical Center, Lackland Air Force Base, TX Defense Institute for Medical Operations, Brooks City-Base, TX Division of Biological Chemistry, Biocentre, Innsbruck Medical University and Ludwig Boltzmann Institute of AIDS-Research, Innsbruck, Austria * Corresponding author; email: boassoa{at}mail.nih.gov. Infection with the human immunodeficiency virus (HIV)-1 results in acute and progressive numerical 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 PBMC from HIV+ patients compared to uninfected healthy controls (HC), and that in vitro inhibition of IDO with the competitive blocker 1-methyl tryptophan (1-mT) results in increased CD4+ T cells proliferative response in PBMC from HIV-infected patients. We developed an in vitro model in which exposure of PBMC from HC to either infectious or noninfectious, R5- or X4-tropic HIV-1 induced IDO in plasmacytoid dendritic cells (pDC). HIV-1-induced IDO was not inhibited by blocking antibodies against interferon type I or type II which, however, induced IDO in pDC when added to PBMC cultures. Blockade of gp120/CD4 interactions with anti-CD4-Ab inhibited HIV-1-mediated IDO induction. Thus, induction of IDO in pDC by HIV-1 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]

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