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Blood, 1 February 2004, Vol. 103, No. 3, pp. 973-979. Prepublished online as a Blood First Edition Paper on October 2, 2003; DOI 10.1182/blood-2003-03-0874. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-03-0874v1 103/3/973    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 Muthukumar, A. Articles by Sodora, D. L. Search for Related Content PubMed PubMed Citation Articles by Muthukumar, A. Articles by Sodora, D. L. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Elevated interleukin-7 levels not sufficient to maintain T-cell homeostasis during simian immunodeficiency virus–induced disease progression Alagarraju Muthukumar, Aneta Wozniakowski, Marie-Claire Gauduin, Mirko Paiardini, Harold M. McClure, R. Paul Johnson, Guido Silvestri, and Donald L. Sodora From the Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas; New England Primate Research Center, Harvard Medical School, Southborough, MA; Yerkes Primate Research Center, Emory University, Atlanta, GA; and Institute of Biochemistry, University of Urbino, Urbino, Italy. Elevated levels of interleukin 7 (IL-7) have been correlated with various T-cell depletion conditions, including HIV infection, and suggested as an indicator of HIV disease progression (AIDS and death). Here, the assessment of pathogenic simian immunodeficiency virus (SIVmac239) infection in rhesus macaques demonstrated a clear association between a significant elevation in IL-7 levels and disease progression. In 5 macaques that progressed to simian AIDS and death, elevated IL-7 levels were unable to restore T-cell homeostasis. In contrast, increased IL-7 levels were followed by relatively high and stable T-cell numbers in the SIV-infected macaques with a slow-progressing phenotype. Further, studies in sooty mangabeys that do not progress to simian AIDS and that maintain stable T-cell numbers despite high levels of viral replication support the importance of IL-7 and T-cell homeostasis in disease progression. These data suggest that during pathogenic SIV infection with high viral replication, elevated IL-7 levels are unable to recover T-cell homeostasis, thereby leading to disease progression. The utility of IL-7 as a potential immunotherapeutic agent to improve HIV/SIV-related T-cell depletion may therefore depend on controlling the pathogenic effects of viral replication prior to the administration of IL-7. (Blood. 2004;103:973-979) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. D. Estes, S. N. Gordon, M. Zeng, A. M. Chahroudi, R. M. Dunham, S. I. Staprans, C. S. Reilly, G. Silvestri, and A. T. Haase Early Resolution of Acute Immune Activation and Induction of PD-1 in SIV-Infected Sooty Mangabeys Distinguishes Nonpathogenic from Pathogenic Infection in Rhesus Macaques J. Immunol., May 15, 2008; 180(10): 6798 - 6807. [Abstract] [Full Text] [PDF] S. N. Gordon, R. M. Dunham, J. C. Engram, J. Estes, Z. Wang, N. R. Klatt, M. Paiardini, I. V. Pandrea, C. Apetrei, D. L. Sodora, et al. Short-Lived Infected Cells Support Virus Replication in Sooty Mangabeys Naturally Infected with Simian Immunodeficiency Virus: Implications for AIDS Pathogenesis J. Virol., April 1, 2008; 82(7): 3725 - 3735. [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] A. S. Albuquerque, C. S. Cortesao, R. B. Foxall, R. S. Soares, R. M. M. Victorino, and A. E. Sousa Rate of Increase in Circulating IL-7 and Loss of IL-7R{alpha} Expression Differ in HIV-1 and HIV-2 Infections: Two Lymphopenic Diseases with Similar Hyperimmune Activation but Distinct Outcomes J. Immunol., March 1, 2007; 178(5): 3252 - 3259. [Abstract] [Full Text] [PDF] S. VandeWoude and C. Apetrei Going Wild: Lessons from Naturally Occurring T-Lymphotropic Lentiviruses Clin. Microbiol. Rev., October 1, 2006; 19(4): 728 - 762. [Abstract] [Full Text] [PDF] L. Swainson, E. Verhoeyen, F.-L. Cosset, and N. Taylor IL-7R{alpha} Gene Expression Is Inversely Correlated with Cell Cycle Progression in IL-7-Stimulated T Lymphocytes. J. Immunol., June 1, 2006; 176(11): 6702 - 6708. [Abstract] [Full Text] [PDF] A. Muthukumar, D. Zhou, M. Paiardini, A. P. Barry, K. S. Cole, H. M. McClure, S. I. Staprans, G. Silvestri, and D. L. Sodora Timely triggering of homeostatic mechanisms involved in the regulation of T-cell levels in SIVsm-infected sooty mangabeys Blood, December 1, 2005; 106(12): 3839 - 3845. [Abstract] [Full Text] [PDF] J.-D. Lelievre, F. Petit, D. Arnoult, J.-C. Ameisen, and J. Estaquier Interleukin 7 Increases Human Immunodeficiency Virus Type 1 LAI-Mediated Fas-Induced T-Cell Death J. Virol., March 1, 2005; 79(5): 3195 - 3199. [Abstract] [Full Text] [PDF] L. J. Picker, S. I. Hagen, R. Lum, E. F. Reed-Inderbitzin, L. M. Daly, A. W. Sylwester, J. M. Walker, D. C. Siess, M. Piatak Jr., C. Wang, et al. Insufficient Production and Tissue Delivery of CD4+ Memory T Cells in Rapidly Progressive Simian Immunodeficiency Virus Infection J. Exp. Med., November 15, 2004; 200(10): 1299 - 1314. [Abstract] [Full Text] [PDF]

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