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Blood, 18 June 2009, Vol. 113, No. 25, pp. 6304-6314. Prepublished online as a Blood First Edition Paper on April 20, 2009; DOI 10.1182/blood-2008-10-186601. This Article Full Text (PDF) Supplemental Appendix, Tables, and Figures All Versions of this Article: blood-2008-10-186601v1 113/25/6304    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 Sereti, I. Articles by Lederman, M. M. Search for Related Content PubMed PubMed Citation Articles by Sereti, I. Articles by Lederman, M. M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 28, 2008 Accepted April 4, 2009 IL-7 administration drives T cell cycle entry and expansion in HIV-1 infection Irini Sereti*, Richard M. Dunham, John Spritzler, Evgenia Aga, Michael A. Proschan, Kathy Medvik, Catherine A. Battaglia, Alan L. Landay, Savita Pahwa, Margaret A. Fischl, David M. Asmuth, Allan R. Tenorio, John D. Altman, Lawrence Fox, Susan Moir, Angela Malaspina, Michel Morre, Renaud Buffet, Guido Silvestri, and Michael M. Lederman National Institutes of Allergy and Infectious Diseases (NIAID), Bethesda, MD, United States University of Pennsylvania, Philadelphia, PA, United States Statistical and Data Analysis Center, Harvard School of Public Health, Boston, MA, United States Case Western Reserve University, University Hospitals/Case Medical Center, Cleveland, OH, United States AIDS Clinical Trial Group Operations Center, Silver Spring, MD, United States Rush University Medical Center, Chicago, IL, United States University of Miami Miller School of Medicine, Miami, FL, United States University of California, Davis Medical Center, Sacramento, CA, United States Emory Vaccine Center, Emory University, Atlanta, GA, United States Division of AIDS, National Institutes of Allergy and Infectious Diseases, Bethesda, MD, United States Cytheris, Paris, France * Corresponding author; email: isereti{at}niaid.nih.gov. Interleukin 7 (IL-7) is a common gamma chain receptor cytokine implicated in thymopoiesis and in peripheral expansion and survival of T lymphocytes. The safety and activity of recombinant human (rh) IL-7 administration was therefore examined in HIV-infected persons. In this prospective randomized placebo-controlled study, a single subcutaneous dose of rhIL-7 was well tolerated with biologic activity demonstrable at 3 µg/kg and a maximum tolerated dose of 30 µg/kg. Injection site reactions and transient elevations of liver function tests were the most notable side effects. Transient increases in plasma HIV-RNA levels were observed in 6/11 IL-7-treated patients. Recombinant hIL-7 induced CD4 and CD8 T cells to enter cell cycle; cell cycle entry was also confirmed in antigen-specific CD8 T cells. Administration of rhIL-7 led to transient downregulation of the IL-7 receptor alpha chain (CD127) in both CD4+ and CD8+ T cells. Single dose rhIL-7 increased the numbers of circulating CD4+ and CD8+ T cells, predominantly of central memory phenotype. The frequency of CD4+ T cells with a regulatory T cell phenotype (CD25high CD127low) did not change after rhIL-7 administration. Thus, rhIL-7 has a biologic and toxicity profile suggesting a potential for therapeutic trials in HIV infection and other settings of lymphopenia. These clinical trials have been registered at www.clinicaltrials.gov under NCT0099671. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Sereti Where have all the T cells gone? Blood, July 23, 2009; 114(4): 751 - 752. [Full Text] [PDF]

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