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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4272-4279. Prepublished online as a Blood First Edition Paper on February 8, 2007; DOI 10.1182/blood-2006-11-055764. This Article Full Text (PDF) All Versions of this Article: blood-2006-11-055764v1 109/10/4272    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 Biancotto, A. Articles by Lederman, M. M. Search for Related Content PubMed PubMed Citation Articles by Biancotto, A. Articles by Lederman, M. M. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 6, 2006 Accepted January 26, 2007 Abnormal activation and cytokine spectra in lymph nodes of persons chronically infected with HIV-1 Angelique Biancotto, Jean-Charles Grivel, Sarah J Iglehart, Christophe Vanpouille, Andrea Lisco, Scott F. Sieg, Robert Debernardo, Kristen Garate, Benigno Rodriguez, Leonid B. Margolis*, and Michael M. Lederman Laboratory of Molecular and Cellular Biophysics, National Institute of Child Health and Human Development, Bethesda, MD, United States Center for AIDS Research, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH, United States * Corresponding author; email: margolis{at}helix.nih.gov. There is growing recognition that HIV-1 infection leads to an activation of the immune system, that includes perturbations of cytokine expression, redistribution of lymphocyte subpopulations, cell dysfunction and cell death. Here we explored the relationships between HIV-1 infection and immune activation in chronically HIV-1 infected human lymph nodes. In addition to CD4 T cell depletion, we found increased effector T cell frequencies associated with profound upregulation of an activation marker CD38 in naive, central memory and effector CD4+ and CD8+ T cells. Likewise, Fas death receptor (CD95) was more frequently detectable on T cells from HIV+ nodes. Dendritic cell depletion was dramatic with PDC 40 fold and MDC 20 fold less frequent in HIV+ nodes than in control nodes. Cytokine dysregulation was evident with IL-2 and IL-15 as much as 2 or 3 logs greater in infected nodes than in control nodes. Thus, activated effector cells are inappropriately attracted and/or retained in lymphoid tissue in chronic HIV-1 infection. High level cytokine expression in turn activates and retains more cells at these sites leading to lymphadenopathy and massive bystander activation that characterizes HIV-1 infection. Strategies targeting these activation pathways may lead to new therapies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Looking at HIV-infected lymph nodes Zvi Grossman Blood 2007 109: 4116-4117. [Full Text] [PDF] This article has been cited by other articles: 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. 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[Abstract] [Full Text] [PDF] A. Biancotto, S. J. Iglehart, C. Vanpouille, C. E. Condack, A. Lisco, E. Ruecker, I. Hirsch, L. B. Margolis, and J.-C. Grivel HIV-1 induced activation of CD4+ T cells creates new targets for HIV-1 infection in human lymphoid tissue ex vivo Blood, January 15, 2008; 111(2): 699 - 704. [Abstract] [Full Text] [PDF] J. Chehimi, L. Azzoni, M. Farabaugh, S. A. Creer, C. Tomescu, A. Hancock, A. Mackiewicz, L. D'Alessandro, S. Ghanekar, A. S. Foulkes, et al. Baseline Viral Load and Immune Activation Determine the Extent of Reconstitution of Innate Immune Effectors in HIV-1-Infected Subjects Undergoing Antiretroviral Treatment J. Immunol., August 15, 2007; 179(4): 2642 - 2650. [Abstract] [Full Text] [PDF]

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