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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3834-3842. Prepublished online as a Blood First Edition Paper on August 8, 2006; DOI 10.1182/blood-2006-04-010637. This Article Full Text (PDF) All Versions of this Article: blood-2006-04-010637v1 108/12/3834    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 Hryniewicz, A. Articles by Franchini, G. Search for Related Content PubMed PubMed Citation Articles by Hryniewicz, A. Articles by Franchini, G. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 12, 2006 Accepted July 17, 2006 CTLA-4 blockade decreases TGF-, indoleamine 2,3- dioxygenase, 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* Animal Models & Retroviral Vaccines Section, National Cancer Institute, Bethesda, Maryland Experimental Immunology Branch, National Cancer Institute, Bethesda, Maryland Division of Biological Chemistry, Biocentre, Innsbruck Medical University, Innsbruck, Austria Biostatistics and Data Management Section, National Cancer Institute, Bethesda, Maryland Department of Microbiology, University of Pennsylvania, Philadelphia, PA Southern Research Institute, Frederick, Maryland Medarex, Bloomsbury, New Jersey Molecular Immunology Section, Children's Hospital Research Foundation, University of Cincinnati * Corresponding author; email: franchig{at}mail.nih.gov. Regulatory T cells (Treg) are a subset of CD25+CD4+ T cells that constitutively express high levels of cytotoxic T lymphocyte antigen-4 (CTLA-4) and suppress T cell activation and effector functions. Treg are increased in tissues of HIV-1-infected individuals and SIVmac-infected (SIV = simian immunodeficiency virus) macaques. In HIV-1 infection, Treg could exert contrasting effects: they may limit viral replication by decreasing immune activation, or they may increase viral replication by suppressing virus-specific immune response. Thus, the outcome of blocking Treg function in HIV/SIV should be empirically tested. Here, we demonstrate that CD25+ T cells inhibit virus-specific T cell responses in cultured T cells from blood and lymph nodes of SIV-infected macaques. We investigated the impact of CTLA-4 blockade using the MDX-010 anti-CTLA-4 human antibody in SIV-infected macaques treated with ART. CTLA-4 blockade decreased expression of the tryptophan-depleting enzyme indoleamine 2,3-dioxygenase (IDO) and the level of the suppressive cytokine TGF- in tissues. CTLA-4 blockade was associated with decreased viral RNA levels in lymph nodes and an increase in the effector function of both SIV-specific CD4+ and CD8+ T cells. Therefore, blunting Treg function in SIV-infected macaques did not have detrimental virological effects and may provide a valuable approach to complement ART and therapeutic vaccination in the treatment of HIV-1 infection. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: HIV 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 Blood 2007 109: 3351-3359. [Abstract] [Full Text] [PDF] This article has been cited by other articles: D. E. Kaufmann and B. D. Walker PD-1 and CTLA-4 Inhibitory Cosignaling Pathways in HIV Infection and the Potential for Therapeutic Intervention J. Immunol., May 15, 2009; 182(10): 5891 - 5897. [Abstract] [Full Text] [PDF] G. Koopman, D. Mortier, S. Hofman, M. Koutsoukos, W. M. J. M. Bogers, B. Wahren, G. Voss, and J. L. Heeney Acute-phase CD4+ T-cell proliferation and CD152 upregulation predict set-point virus replication in vaccinated simian-human immunodeficiency virus strain 89.6p-infected macaques J. Gen. Virol., April 1, 2009; 90(4): 915 - 926. [Abstract] [Full Text] [PDF] A. Boasso, M. Vaccari, D. Fuchs, A. W. Hardy, W.-P. Tsai, E. Tryniszewska, G. M. Shearer, and G. Franchini Combined Effect of Antiretroviral Therapy and Blockade of IDO in SIV-Infected Rhesus Macaques J. Immunol., April 1, 2009; 182(7): 4313 - 4320. [Abstract] [Full Text] [PDF] A. Ribas, B. Comin-Anduix, J. S. Economou, T. R. 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Boasso, J.-P. Herbeuval, A. W. Hardy, S. A. Anderson, M. J. Dolan, D. Fuchs, and G. M. Shearer HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells Blood, April 15, 2007; 109(8): 3351 - 3359. [Abstract] [Full Text] [PDF] A. Hryniewicz, D. A. Price, M. Moniuszko, A. Boasso, Y. Edghill-Spano, S. M. West, D. Venzon, M. Vaccari, W.-P. Tsai, E. Tryniszewska, et al. Interleukin-15 but Not Interleukin-7 Abrogates Vaccine-Induced Decrease in Virus Level in Simian Immunodeficiency Virusmac251-Infected Macaques J. Immunol., March 15, 2007; 178(6): 3492 - 3504. [Abstract] [Full Text] [PDF]

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