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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2458-2464. Prepublished online as a Blood First Edition Paper on December 7, 2004; DOI 10.1182/blood-2004-08-3058. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-08-3058v1 105/6/2458    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 Herbeuval, J.-P. Articles by Shearer, G. M. Search for Related Content PubMed PubMed Citation Articles by Herbeuval, J.-P. Articles by Shearer, G. M. 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 TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1–infected patients and its in vitro production by antigen-presenting cells Jean-Philippe Herbeuval, Adriano Boasso, Jean-Charles Grivel, Andrew W. Hardy, Stephanie A. Anderson, Matthew J. Dolan, Claire Chougnet, Jeffrey D. Lifson, and Gene M. Shearer From the Experimental Immunology Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD; Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, MD; Henry M. Jackson Foundation and Infectious Diseases Service, Wilford Hall Medical Center, Lackland Air Force Base, TX; Division of Molecular Immunology, Children's Hospital Research Foundation, Cincinnati, OH; and AIDS Vaccine Program, Science Applications International Corporation (SAIC) Frederick, NCI-Frederick, MD. There is now considerable in vitro evidence that tumor necrosis factor (TNF)–related apoptosis-inducing ligand (TRAIL) is involved in HIV-1 pathogenesis by inducing CD4+ T-cell death characteristic of AIDS. Therefore, we have tested levels of TRAIL in plasma samples from 107 HIV-1–infected and 53 uninfected controls as well as in longitudinal plasma samples from patients who started antiret-roviral therapy (ART). TRAIL was elevated in plasma of HIV-1–infected patients compared with uninfected individuals, and patients receiving ART showed decreased plasma TRAIL levels that correlated with reduction in viral load. In vitro exposure to infectious and noninfectious HIV-1 induced TRAIL in monocytes and marginally in dendritic cells (DCs) but not in macrophages or T cells. Interestingly, the HIV-1 entry inhibitor, soluble CD4, blocked HIV-1–induced production of TRAIL. Furthermore, production and gene expression of TRAIL by monocytes were regulated by type I interferon via signal transducer and activator of transcription-1 (STAT1)/STAT2 signaling molecule. Ex vivo HIV-1 infection of human tonsil lymphoid tissue also resulted in increased TRAIL production. We demonstrate here that plasma TRAIL is elevated in HIV-1–infected patients and is decreased by ART therapy. The high production of TRAIL by antigen-presenting cells may contribute to the death of CD4+ T cells during progression to AIDS. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: On the TRAIL of HIV-induced immunosuppression Pierre-Olivier Vidalain Blood 2005 105: 2241. [Full Text] [PDF] This article has been cited by other articles: N. Gasper-Smith, D. M. Crossman, J. F. Whitesides, N. Mensali, J. S. Ottinger, S. G. Plonk, M. A. Moody, G. Ferrari, K. J. Weinhold, S. E. Miller, et al. Induction of Plasma (TRAIL), TNFR-2, Fas Ligand, and Plasma Microparticles after Human Immunodeficiency Virus Type 1 (HIV-1) Transmission: Implications for HIV-1 Vaccine Design J. Virol., August 1, 2008; 82(15): 7700 - 7710. [Abstract] [Full Text] [PDF] R. Stefanescu, D. Bassett, R. Modarresi, F. Santiago, M. Fakruddin, and J. Laurence Synergistic interactions between interferon-{gamma} and TRAIL modulate c-FLIP in endothelial cells, mediating their lineage-specific sensitivity to thrombotic thrombocytopenic purpura plasma-associated apoptosis Blood, July 15, 2008; 112(2): 340 - 349. [Abstract] [Full Text] [PDF] J.-P. Herbeuval, J.-C. Grivel, A. Boasso, A. W. Hardy, C. Chougnet, M. J. Dolan, H. Yagita, J. D. Lifson, and G. M. Shearer CD4+ T-cell death induced by infectious and noninfectious HIV-1: role of type 1 interferon-dependent, TRAIL/DR5-mediated apoptosis Blood, November 15, 2005; 106(10): 3524 - 3531. [Abstract] [Full Text] [PDF]

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