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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3524-3531. Prepublished online as a Blood First Edition Paper on July 26, 2005; DOI 10.1182/blood-2005-03-1243. This Article Full Text (PDF) All Versions of this Article: 2005-03-1243v1 106/10/3524    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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 28, 2005 Accepted July 18, 2005 CD4+ T cell death induced by infectious and noninfectious HIV-1: role of type I interferon-dependent, TRAIL/DR5-mediated apoptosis Jean-Philippe Herbeuval, Jean-Charles Grivel, Adriano Boasso, Andrew W Hardy, Claire Chougnet, Matthew J Dolan, Hideo Yagita, Jeffrey D Lifson, and Gene M Shearer* Experimental Immunology Branch, NCI, NIH, Bethesda, MD, USA Laboratory of Cellular and Molecular Biophysics, NICHHD, NIH, Bethesda, MD, USA Division of Molecular Immunology, Children's Hospital Research Foundation, Cincinnati, OH, USA Infectious Diseases Service, Wilford Hall Medical Center, Lackland, TX, USA Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan AIDS Vaccine Program, SAIC Frederick, Inc., NCI-Frederick, Frederick, MD, USA * Corresponding author; email: shearerg{at}mail.nih.gov. Both direct and indirect mechanisms have been proposed to contribute to the unresolved issue of CD4+ T cell depletion that results from HIV-1 infection. We recently reported that plasma levels of TNF-Related Apoptosis-Inducing Ligand (TRAIL) are elevated in HIV-1-infected patients, and correlate with viral load. The present study investigates the expression of TRAIL death receptor 5 (DR5) in PBMC from HIV-1-infected patients and its role in CD4+ T cell death. DR5 expression was elevated and associated with the apoptotic marker Annexin V. Apoptosis was reduced in patients' CD4+ T cells when cultured with anti-DR5 antibody. CD4+ but not CD8+ T cells from uninfected donors expressed TRAIL, DR5 and activated caspase-3 when cultured with infectious or noninfectious HIV-1, resulting in preferential apoptosis of CD4+ T cells. TRAIL, caspase-3 expression and apoptosis were type I interferon-dependent. Induction of apoptosis and DR5 expression required gp120-CD4 interaction. Finally, we analyzed DR5 expression by CD4+ T cells in HAART treated patients. The decreased viral loads and increased CD4 counts of HAART-responsive patients were associated with a decrease in DR5 mRNA expression by CD4+ T lymphocytes. We propose a novel model in which a type I interferon-regulated TRAIL/DR5 mechanism induces apoptosis of HIV-1-exposed CD4+ T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? 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. S. Veazey, P. M. Acierno, K. J. McEvers, S. H. C. Baumeister, G. J. Foster, M. D. 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Boasso, A. W. Hardy, M. J. Kruhlak, S. A. Anderson, M. J. Dolan, M. Dy, J. Andersson, and G. M. Shearer Differential expression of IFN-{alpha} and TRAIL/DR5 in lymphoid tissue of progressor versus nonprogressor HIV-1-infected patients PNAS, May 2, 2006; 103(18): 7000 - 7005. [Abstract] [Full Text] [PDF]

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