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Prepublished online as a Blood First Edition Paper on July 5, 2002; DOI 10.1182/blood-2001-12-0293. This Article Full Text (PDF) All Versions of this Article: 2001-12-0293v1 100/10/3633    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 Cooper, M. A Articles by Caligiuri, M. A Search for Related Content PubMed PubMed Citation Articles by Cooper, M. A Articles by Caligiuri, M. A Social Bookmarking                   What's this? Submitted December 21, 2001 Accepted June 19, 2002 In vivo evidence for a dependence on interleukin-15 for natural killer cell survival Megan A Cooper, Jennifer E Bush, Todd A Fehniger, Jeffrey B VanDeusen, Ross E Waite, Yang Liu, Hector L Aguila, and Michael A Caligiuri* Department of Internal Medicine, Division of Hematology and Oncology, Ohio State University, Columbus, OH, USA; Department of Veterinary Biosciences, Ohio State University, Columbus, OH, USA Department of Internal Medicine, Division of Hematology and Oncology, Ohio State University, Columbus, OH, USA Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus, OH, USA; Department of Internal Medicine, Division of Hematology and Oncology, Ohio State University, Columbus, OH, USA Department of Pathology, Ohio State University, Columbus, OH, USA Center for Immunotherapy, University of Connecticut Health Center, Farmington, CT, USA Department of Internal Medicine, Division of Hematology and Oncology, Ohio State University, Columbus, OH, USA; Department of Veterinary Biosciences, Ohio State University, Columbus, OH, USA; Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus, OH, USA * Corresponding author; email: Caligiuri-1{at}medctr.osu.edu. Cellular homeostasis requires a balance between cell production, cell survival, and cell death. Natural killer (NK) cell production from bone marrow precursor cells requires IL-15, however very little is known about the factors controlling mature NK cell survival in vivo. As mice deficient in IL-15 (IL-15-/-) fail to develop NK cells, it is not known whether mature NK cells can survive in an environment lacking IL-15. We hypothesize that IL-15 might indeed be required for mature NK cell survival in vivo. Freshly isolated, CFSE-labeled, NK cells were adoptively transferred into IL-15-/- and littermate control (IL-15+/-) mice. Within 36 hr after transfer, NK cells were detected in both IL-15-/- and IL-15+/- mice; however significantly more (p<0.003) CFSE+ NK cells were found in control as opposed to IL-15-/- mice. By 5 days, similar numbers of CFSE+ NK cells still were easily detected in IL-15+/- animals, whereas no CFSE+ NK cells survived in IL-15-/- mice. Further, SCID mice treated with the Fab fragment of a blocking antibody recognizing a signaling subunit of the IL-15 receptor, IL-2/15Rß, had a significant (~90%) loss of NK cells compared to control-treated mice. Finally, NK cells from bcl-2 transgenic mice that were adoptively transferred into IL-15-/- mice did survive. These results conclusively demonstrate that IL-15 is required for mature NK cell survival in vivo and suggest that IL-15 mediates its effect on NK cell survival via Bcl-2. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. F. Castillo, S. W. Stonier, L. Frasca, and K. S. Schluns Dendritic Cells Support the In Vivo Development and Maintenance of NK Cells via IL-15 Trans-Presentation J. Immunol., October 15, 2009; 183(8): 4948 - 4956. [Abstract] [Full Text] [PDF] J. C. Sun, A. Ma, and L. L. Lanier Cutting Edge: IL-15-Independent NK Cell Response to Mouse Cytomegalovirus Infection J. 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