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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3571-3578. Prepublished online as a Blood First Edition Paper on January 15, 2008; DOI 10.1182/blood-2007-07-100057. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-07-100057v1 111/7/3571    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 CrossRef Google Scholar Articles by Coudert, J. D. Articles by Held, W. PubMed PubMed Citation Articles by Coudert, J. D. Articles by Held, W. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Sustained NKG2D engagement induces cross-tolerance of multiple distinct NK cell activation pathways Jérôme D. Coudert1, Léonardo Scarpellino1, Frédéric Gros1, Eric Vivier2,4, and Werner Held1 1 Ludwig Institute for Cancer Research, Lausanne Branch and University of Lausanne, Switzerland; 2 Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, Marseille, France; 3 Inserm, U631, Marseille, France; and 4 Centre National de la Recherche Scientifique (CNRS), UMR6102, Marseille, France NKG2D is a multisubunit activation receptor that allows natural killer (NK) cells to detect and eliminate stressed, infected, and transformed host cells. However, the chronic exposure of NK cells to cell-bound NKG2D ligands has been shown to impair NKG2D function both in vitro and in vivo. Here we have tested whether continuous NKG2D engagement selectively impacted NKG2D function or whether heterologous NK cell activation pathways were also affected. We found that sustained NKG2D engagement induced cross-tolerization of several unrelated NK cell activation receptors. We show that receptors that activate NK cells via the DAP12/KARAP and DAP10 signaling adaptors, such as murine NKG2D and Ly49D, cross-tolerize preferentially NK cell activation pathways that function independent of DAP10/12, such as antibody-dependent cell-mediated cytotoxicity and missing-self recognition. Conversely, DAP10/12-independent pathways are unable to cross-tolerize unrelated NK cell activation receptors such as NKG2D or Ly49D. These data define a class of NK cell activation receptors that can tolerize mature NK cells. The reversible suppression of the NK cells' cytolytic function probably reduces the NK cells' efficacy to control endogenous and exogenous stress yet may be needed to limit tissue damage. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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