SEARCH:   Advanced

Blood, 15 May 2006, Vol. 107, No. 10, pp. 3992-3999. Prepublished online as a Blood First Edition Paper on January 31, 2006; DOI 10.1182/blood-2005-09-3851. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-09-3851v1 107/10/3992    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 Bianchi, T. Articles by MacDonald, H. R. Search for Related Content PubMed PubMed Citation Articles by Bianchi, T. Articles by MacDonald, H. R. Related Collections Immunobiology Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY c-Myc acts downstream of IL-15 in the regulation of memory CD8 T-cell homeostasis Teresa Bianchi, Stephan Gasser, Andreas Trumpp, and H. Robson MacDonald From the Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne; Swiss Institute for Experimental Cancer Research, Epalinges; and Genetics and Stem Cell Laboratory, Swiss Institute for Experimental Cancer Research and Swiss Institute of Technology Lausanne, Epalinges, Switzerland. A subset of CD8 T cells in normal mice, expressing high levels of activation markers such as CD44, shares many properties with antigen-specific memory CD8 T cells. Homeostasis of CD44high CD8 T cells depends upon cytokines such as interleukin-15 (IL-15); however, the downstream signaling pathways regulating IL-15–dependent homeostatic proliferation are poorly defined. Surprisingly, we show here that haploinsufficiency of the protooncogene c-myc leads to a highly selective decrease in CD44high CD8 T cells in mice. Although steady-state proliferation and survival of CD44high CD8 T cells appeared not to be dependent on c-Myc, homeostatic proliferation of c-myc+/– CD44high CD8 T cells in lymphopenic hosts was strongly reduced, and the residual homeostatic proliferation of these cells appeared to occur independently of IL-15. Moreover, c-myc+/– CD44high CD8 T cells responded very poorly to purified IL-15 in vitro. Backcrossing of c-myc+/– mice to IL-15–/– mice revealed that the number of CD44high CD8 T cells decreased in an additive fashion in mice heterozygous for c-myc and IL-15. Finally homeostatic proliferation of antigen-specific memory CD44high CD8 T cells was also impaired in c-myc+/– mice. Collectively, our data identify c-Myc as a novel downstream component of the IL-15–dependent pathway controlling homeostatic proliferation of memory CD44high CD8 T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. P. Mycko, I. Ferrero, A. Wilson, W. Jiang, T. Bianchi, A. Trumpp, and H. R. MacDonald Selective Requirement for c-Myc at an Early Stage of V{alpha}14i NKT Cell Development J. Immunol., April 15, 2009; 182(8): 4641 - 4648. [Abstract] [Full Text] [PDF] F. Cichocki, R. J. Hanson, T. Lenvik, M. Pitt, V. McCullar, H. Li, S. K. Anderson, and J. S. Miller The transcription factor c-Myc enhances KIR gene transcription through direct binding to an upstream distal promoter element Blood, April 2, 2009; 113(14): 3245 - 3253. [Abstract] [Full Text] [PDF] E. Merck, R. B. Voyle, and H. R. MacDonald Ly49D Engagement on T Lymphocytes Induces TCR-Independent Activation and CD8 Effector Functions That Control Tumor Growth J. Immunol., January 1, 2009; 182(1): 183 - 192. [Abstract] [Full Text] [PDF] K. Nakazato, H. Yamada, T. Yajima, Y. Kagimoto, H. Kuwano, and Y. Yoshikai Enforced Expression of Bcl-2 Partially Restores Cell Numbers but Not Functions of TCR{gamma}{delta} Intestinal Intraepithelial T Lymphocytes in IL-15-Deficient Mice J. Immunol., January 15, 2007; 178(2): 757 - 764. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020