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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 (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 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 Social Bookmarking                   What's this? Submitted July 31, 2002 Accepted October 20, 2002 IL-7 therapy dramatically alters peripheral T-cell homeostasis in normal and SIV-infected non-human 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 Pediatric Oncology Branch, Center for Cancer Research, Bethesda, MD, USA Animal Model and Retrovirus Vaccine Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Biological Resources Branch, National Cancer Institute, National Institutes of Health, Frederick, MD, USA Toxicology and Pharmacology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA Vaccine Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA Biopharmaceutical Development Program, Science Applications International Corp. Frederick, National Cancer Institute, National Institutes of Health, Frederick, MD, USA Intramural Research Support Program, National Cancer Institute, National Institutes of Health, Frederick, MD, USA * Corresponding author; email: tf60y{at}nih.gov. Interleukin 7 is important for thymopoiesis in mice and humans since 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 rhIL-7 therapy in normal and SIV infected non-human 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 non-naive 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 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 <5% to approximately 50% after 6 days of therapy) and ex vivo 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, rhIL7 induces dramatic alterations in peripheral T cell homeostasis in both T cell replete and T cell depleted non-human 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. 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