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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 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 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 Google Scholar Articles by Sereti, I. Articles by Lederman, M. M. PubMed PubMed Citation Articles by Sereti, I. Articles by Lederman, M. M. Related Collections Immunobiology Free Research Articles Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL TRIALS AND OBSERVATIONS IL-7 administration drives T cell–cycle entry and expansion in HIV-1 infection Irini Sereti1, Richard M. Dunham2, John Spritzler3, Evgenia Aga3, Michael A. Proschan1, Kathy Medvik4, Catherine A. Battaglia5, Alan L. Landay6, Savita Pahwa7, Margaret A. Fischl7, David M. Asmuth8, Allan R. Tenorio6, John D. Altman9, Lawrence Fox10, Susan Moir1, Angela Malaspina1, Michel Morre11, Renaud Buffet11, Guido Silvestri2, Michael M. Lederman4, for the ACTG 5214 Study Team 1 National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, MD; 2 University of Pennsylvania, Philadelphia; 3 Statistical and Data Analysis Center, Harvard School of Public Health, Boston, MA; 4 Case Western Reserve University, University Hospitals/Case Medical Center, Cleveland, OH; 5 AIDS Clinical Trial Group Operations Center, Silver Spring, MD; 6 Rush University Medical Center, Chicago, IL; 7 University of Miami Miller School of Medicine, FL; 8 University of California, Davis Medical Center, Sacramento; 9 Emory Vaccine Center, Emory University, Atlanta, GA; 10 Division of AIDS, NIAID, Bethesda, MD; and 11 Cytheris, Paris, France 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 IL-7 (rhIL-7) administration were 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 of 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 down-regulation 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. This clinical trial has been registered at http://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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