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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2381-2389. Prepublished online as a Blood First Edition Paper on June 23, 2008; DOI 10.1182/blood-2007-12-127779. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-12-127779v1 112/6/2381    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 Fourmentraux-Neves, E. Articles by Caignard, A. Search for Related Content PubMed PubMed Citation Articles by Fourmentraux-Neves, E. Articles by Caignard, A. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Two opposite signaling outputs are driven by the KIR2DL1 receptor in human CD4+ T cells Emmanuelle Fourmentraux-Neves1, Abdelali Jalil1, Sylvie Da Rocha1, Christophe Pichon1, Salem Chouaib1, Georges Bismuth2, and Anne Caignard1,2 1 Inserm U753, Institut Gustave Roussy, Villejuif; and 2 Inserm U567, Institut Cochin, Paris, France Inhibitory killer Ig–like receptors (KIR), expressed by human natural killer cells and effector memory CD8+ T-cell subsets, bind HLA-C molecules and suppress cell activation through recruitment of the Src homology 2 domain-containing protein tyrosine phosphatase 1 (SHP-1). To further analyze the still largely unclear role of inhibitory KIR receptors on CD4+ T cells, KIR2DL1 transfectants were obtained from a CD4+ T-cell line and primary cells. Transfection of CD4+ T cells with KIR2DL1 dramatically increased the T-cell receptor (TCR)–induced production of interleukin-2 independently of ligand binding but inhibited TCR-induced activation after ligation. KIR-mediated costimulation of TCR activation involves intact KIR2DL1-ITIM phosphorylation, SHP-2 recruitment, and PKC- phosphorylation. Synapses leading to activation were characterized by an increase in the recruitment of p-Tyr, SHP-2, and p-PKC-, but not of SHP-1. Interaction of KIR2DL1 with its ligand led to a strong synaptic accumulation of KIR2DL1 and the recruitment of SHP-1/2, inhibiting TCR-induced interleukin-2 production. KIR2DL1 may induce 2 opposite signaling outputs in CD4+ T cells, depending on whether the KIR receptor is bound to its ligand. These data highlight unexpected aspects of the regulation of T cells by KIR2DL1 receptors, the therapeutic manipulation of which is currently being evaluated. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Li, M. Yu, C. M. Weyand, and J. J. Goronzy Epigenetic regulation of killer immunoglobulin-like receptor expression in T cells Blood, October 15, 2009; 114(16): 3422 - 3430. [Abstract] [Full Text] [PDF]

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