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Blood, 15 November 2004, Vol. 104, No. 10, pp. 3267-3275.
Prepublished online as a Blood First Edition Paper on July 8, 2004; DOI 10.1182/blood-2004-01-0380.


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Submitted January 29, 2004
Accepted June 1, 2004

NK Cell Activation by Dendritic Cells (DC) Require The Formation of a Synapse leading to IL-12 Polarization in DC

Christophe Borg*, Jalil Abdelali, Diego Laderach, Kouji Maruyama, Hiro Wakasugi, Sabine Charrier, Bernhard Ryffel, William Vainchenker, Anne Galy, Anne Caignard, Laurence Zitvogel, Alessandra Cambi, and Carl Figdor

ERM0208 INSERM, Department of Clinical Biology, Institut Gustave Roussy, Villejuif, Val de marne, France
U487 INSERM, Institut Gustave Roussy, Villejuif, France
U362 INSERM, Institut Gustave Roussy, Villejuif, France; Genethon, Evry, Val de marne, France
Pharmacology Division, National Cancer Center, Tokyo, Japan
GEM2358, CNRS, Orleans, France
U362 INSERM, Institut Gustave Roussy, Villejuif, France
University Medical Center, Nijmegen, The Netherlands

* Corresponding author; email: christophe.borg{at}wanadoo.fr.

Mature dendritic cells (DC) can trigger the effector functions of natural killer (NK) cells. Knock-out, small interfering RNA or neutralizing antibodies targeting IL-12 subunits revealed a critical role for IL-12 in NK cell IFN{gamma} secretion promoted by mature DC. However, NK cell activation by DC also required direct cell-to-cell contacts. DC-mediated NK cell activation involved the formation of stimulatory synapses between DC and NK cells. The formation of DC/NK cell conjugates was found to depend on cytoskeleton remodeling and lipid raft mobilization in DC. Moreover, the disruption of the DC cytoskeleton using pharmacological agents or the loss-of-function mutation of the Wiskott-Aldrich syndrome protein abolished the DC-mediated NK cell activation. Synapse formation promoted the polarized secretion of preassembled stores of IL-12 by DC towards the NK cell. The synaptic delivery of IL-12 by DC was found to be required for IFN{gamma} secretion by NK cells, as assessed using inhibitors of cytoskeleton rearrangements and transwell experiments. Therefore, the cross talk between DC and NK cells is dictated by functional synapses.


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