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Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-07-2297. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-07-2297v1 101/6/2294    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 Fry, T. J. Articles by Mackall, C. L. Search for Related Content PubMed PubMed Citation Articles by Fry, T. J. Articles by Mackall, C. L. Related Collections Immunobiology Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 March 2003, Vol. 101, No. 6, pp. 2294-2299 IMMUNOBIOLOGY IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected nonhuman primates Terry J. Fry, Marcin Moniuszko, Stephen Creekmore, Susan J. Donohue, Daniel C. Douek, Steven Giardina, Toby T. Hecht, Brenna J. Hill, Kristen Komschlies, Joseph Tomaszewski, Genoveffa Franchini, and Crystal L. Mackall From the Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; Animal Model and Retrovirus Vaccine Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD; Developmental Therapeutics Program, Biological Therapy, Division of Cancer Therapy & Diagnosis, National Cancer Institute; Toxicology and Pharmacology Branch, Division of Cancer Therapy & Diagnostics, National Cancer Institute, Bethesda, MD; Vaccine Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; and Biopharmaceutical Development Program, SAIC, Frederick, MD. Interleukin-7 (IL-7) is important for thymopoiesis in mice and humans because IL-7 receptor  (IL-7R) mutations result in a severe combined immunodeficiency phenotype with severe thymic hypoplasia. Recent evidence has indicated that IL-7 also plays an important role as a regulator of T-cell homeostasis. Here we report the immunologic effects of recombinant human IL-7 (rhIL-7) therapy in normal and simian immunodeficiency virus (SIV)-infected nonhuman primates. Cynomolgus monkeys receiving 10 days of rhIL-7 showed substantial, reversible increases in T-cell numbers involving a dramatic expansion of both naive and nonnaive phenotype CD4+ and CD8+ subsets. Although IL-7 is known to have thymopoietic effects in mice, we observed marked declines in the frequency and absolute number of T-cell receptor excision circle-positive (TREC+) cells in the peripheral blood and dramatic increases in the percentage of cycling T cells in the peripheral blood as measured by Ki-67 expression (baseline less than 5% to approximately 50% after 6 days of therapy) and ex vivo bromodeoxyuridine (BrdU) incorporation. Similarly, moderately CD4- depleted SIV-infected macaques treated with rhIL-7 also had significant increases in peripheral blood CD4+ and CD8+ T cells following rhIL-7 therapy. Thus, rhIL-7 induces dramatic alterations in peripheral T-cell homeostasis in both T-cell-replete and T-cell-depleted nonhuman primates. These results further implicate IL-7 as a promising immunorestorative agent but illustrate that a major component of its immunorestorative capacity reflects effects on mature cells. These results also raise the possibility that IL-7 therapy could be used to temporarily modulate T-cell cycling in vivo in the context of immunotherapies such as vaccination. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Beq, S. Rozlan, D. Gautier, R. Parker, V. Mersseman, C. Schilte, B. Assouline, I. Rance, P. Lavedan, M. Morre, et al. 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