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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3808-3817. Prepublished online as a Blood First Edition Paper on August 10, 2006; DOI 10.1182/blood-2006-05-021576. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-05-021576v1 108/12/3808    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 Nilsson, J. Articles by Chougnet, C. Search for Related Content PubMed PubMed Citation Articles by Nilsson, J. Articles by Chougnet, C. Related Collections Immunobiology Clinical Trials and Observations Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY 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 From the Center for Infectious Medicine, Division of Infectious Diseases, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden; the Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; the Division of Molecular Immunology, Cincinnati Children's Hospital Research Foundation and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH; the Immunovirology group, University of Antioquia, Medellin, Colombia; and the Animal Models and Retroviral Vaccines Section, National Cancer Institute, Bethesda, MD. Regulatory T (Treg) cells accumulate in the lymphoid tissues of human immunodeficiency virus (HIV)–infected individuals, contributing to the inability of the immune system to control virus replication. We investigate here Treg-cell numbers and functional markers (FOXP3, CTLA-4, IDO, and TGF-1) in lymphoid tissues from untreated infected hosts with progressive or nonprogressive disease (HIV-infected humans and simian immunodeficiency virus [SIV]–infected macaques). We found that increased numbers of FOXP3+ T cells as well as increased expression of Treg-cell–associated functional markers were detected only during progressive disease. Such increases were not correlated with immune activation. Of importance, a high-perforin/FOXP3 ratio was associated with nonprogressive disease, suggesting that the immune control of virus replication represents a balance between cell-mediated immune responses and Treg-cell–mediated counter regulation of such responses. Furthermore, using an in vitro model of Treg-cell–HIV interactions, we showed that exposure of Treg cells to HIV selectively promoted their survival via a CD4-gp120–dependent pathway, thus providing an underlying mechanism for the accumulation of Treg cells in infected hosts with active viral replication. Considered together, our findings imply that therapeutic manipulation of Treg-cell number and/or function could improve immune control of HIV 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: M. E. Moreno-Fernandez, W. Zapata, J. T. Blackard, G. Franchini, and C. 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Engram, S. Gordon, N. R. Klatt, I. Frank, et al. CD127 and CD25 Expression Defines CD4+ T Cell Subsets That Are Differentially Depleted during HIV Infection J. Immunol., April 15, 2008; 180(8): 5582 - 5592. [Abstract] [Full Text] [PDF] H. Hu, K. Fernando, H. Ni, and D. Weissman HIV Envelope Suppresses CD4+ T Cell Activation Independent of T Regulatory Cells J. Immunol., April 15, 2008; 180(8): 5593 - 5600. [Abstract] [Full Text] [PDF] L. C. Ndhlovu, C. P. Loo, G. Spotts, D. F. Nixon, and F. M. Hecht FOXP3 expressing CD127lo CD4+ T cells inversely correlate with CD38+ CD8+ T cell activation levels in primary HIV-1 infection J. Leukoc. Biol., February 1, 2008; 83(2): 254 - 262. [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] I. Karlsson, B. Malleret, P. Brochard, B. Delache, J. Calvo, R. Le Grand, and B. Vaslin FoxP3+ CD25+ CD8+ T-Cell Induction during Primary Simian Immunodeficiency Virus Infection in Cynomolgus Macaques Correlates with Low CD4+ T-Cell Activation and High Viral Load J. Virol., December 15, 2007; 81(24): 13444 - 13455. [Abstract] [Full Text] [PDF] A. J. Chase, A. R. Sedaghat, J. R. German, L. Gama, M. C. Zink, J. E. Clements, and R. F. Siliciano Severe Depletion of CD4+ CD25+ Regulatory T Cells from the Intestinal Lamina Propria but Not Peripheral Blood or Lymph Nodes during Acute Simian Immunodeficiency Virus Infection J. Virol., December 1, 2007; 81(23): 12748 - 12757. [Abstract] [Full Text] [PDF] S. Balkow, F. Krux, K. Loser, J. U. Becker, S. Grabbe, and U. Dittmer Friend retrovirus infection of myeloid dendritic cells impairs maturation, prolongs contact to naive T cells, and favors expansion of regulatory T cells Blood, December 1, 2007; 110(12): 3949 - 3958. [Abstract] [Full Text] [PDF] A. Boasso, M. Vaccari, A. Hryniewicz, D. Fuchs, J. Nacsa, V. Cecchinato, J. Andersson, G. Franchini, G. M. Shearer, and C. Chougnet Regulatory T-Cell Markers, Indoleamine 2,3-Dioxygenase, and Virus Levels in Spleen and Gut during Progressive Simian Immunodeficiency Virus Infection J. Virol., November 1, 2007; 81(21): 11593 - 11603. [Abstract] [Full Text] [PDF] D. Holmes, G. Knudsen, S. Mackey-Cushman, and L. Su FoxP3 Enhances HIV-1 Gene Expression by Modulating NF{kappa}B Occupancy at the Long Terminal Repeat in Human T Cells J. Biol. Chem., June 1, 2007; 282(22): 15973 - 15980. [Abstract] [Full Text] [PDF] L. E. Pereira, F. Villinger, N. Onlamoon, P. Bryan, A. Cardona, K. Pattanapanysat, K. Mori, S. Hagen, L. Picker, and A. A. Ansari Simian Immunodeficiency Virus (SIV) Infection Influences the Level and Function of Regulatory T Cells in SIV-Infected Rhesus Macaques but Not SIV-Infected Sooty Mangabeys J. Virol., May 1, 2007; 81(9): 4445 - 4456. [Abstract] [Full Text] [PDF] A. 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. Kinter, J. McNally, L. Riggin, R. Jackson, G. Roby, and A. S. Fauci Suppression of HIV-specific T cell activity by lymph node CD25+ regulatory T cells from HIV-infected individuals PNAS, February 27, 2007; 104(9): 3390 - 3395. [Abstract] [Full Text] [PDF]

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