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Blood, 1 March 2005, Vol. 105, No. 5, pp. 2082-2089. Prepublished online as a Blood First Edition Paper on November 9, 2004; DOI 10.1182/blood-2004-08-3262. This Article Full Text (PDF) All Versions of this Article: 2004-08-3262v1 105/5/2082    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 Takeda, K. Articles by Smyth, M. J Search for Related Content PubMed PubMed Citation Articles by Takeda, K. Articles by Smyth, M. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 24, 2004 Accepted November 2, 2004 TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver Kazuyoshi Takeda*, Erika Cretney, Yoshihiro Hayakawa, Tsuyoshi Ota, Hisaya Akiba, Kouetsu Ogasawara, Hideo Yagita, Katsuyoshi Kinoshita, Ko Okumura, and Mark J Smyth Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan; Department of Obstetric and Genecology, Juntendo University School of Medicine, Tokyo, Japan Department of of Microbiology and Immunology, and the Cancer Research Institute, University of California San Francisco, San Francisco, CA, USA Department of Obstetric and Genecology, Juntendo University School of Medicine, Tokyo, Japan * Corresponding author; email: ktakeda{at}med.juntendo.ac.jp. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a key effector molecule expressed by NK cells and has been shown to prevent tumor initiation, growth, and metastasis. Here we demonstrate that TRAIL is the dominant cytotoxic effector molecule expressed by NK cells in fetal mice. Upon birth and with age, NK cells develop full functional capacity, including the ability to secrete IFN- and IL-13, mediate perforin- and Fas ligand-mediated cytotoxicity. However, interestingly, a phenotypically immature TRAIL+ NK cell subpopulation is retained in the liver of adult mice, and its retention is IFN--dependent, but not dependent upon host IL-12, IL-18, or endogenous host pathogens. Adoptive transfer of either adult liver or neonatal TRAIL+ NK cells resulted in the appearance of TRAIL- NK cells with a mature phenotype, suggesting that these TRAIL+ NK cells were indeed a precursor. Although inducers of IFN- stimulated TRAIL expression on mature NK cells, our data indicated that constitutive TRAIL expression was a hallmark of immature cytotoxic NK cells. This study is the first to describe the concomitant maturation of NK cell effector function with surface phenotype in vivo and implies an important defense role for NK cell TRAIL in the developing immune system. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Chiossone, J. Chaix, N. Fuseri, C. Roth, E. Vivier, and T. Walzer Maturation of mouse NK cells is a 4-stage developmental program Blood, May 28, 2009; 113(22): 5488 - 5496. [Abstract] [Full Text] [PDF] S. V. Watt, D. M. Andrews, K. Takeda, M. J. Smyth, and Y. Hayakawa IFN-{gamma}-Dependent Recruitment of Mature CD27high NK Cells to Lymph Nodes Primed by Dendritic Cells J. Immunol., October 15, 2008; 181(8): 5323 - 5330. [Abstract] [Full Text] [PDF] B. M. Burt, G. 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