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Cognate CD4+ T-cell–dendritic cell interactions induce migration of immature dendritic cells through dissolution of their podosomes

Nobile, Cinzia and Lind, Marianne and Miro, Francesc and Chemin, Karine and Tourret, Marie and Occhipinti, Giovanni and Dogniaux, Stéphanie and Amigorena, Sebastian and Hivroz, Claire (2008) Cognate CD4+ T-cell–dendritic cell interactions induce migration of immature dendritic cells through dissolution of their podosomes. Blood, 111 (7). pp. 3579-3590. ISSN 0006-4971. http://resolver.caltech.edu/CaltechAUTHORS:NOBblo08

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Other (Figure S1 (jpeg). DC or LPS-tretaed DC were incubated with CCI and migration towards CCL5 and CXCL12 was analyzed by transwell assay)
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[img] Other (Video 1 (.avi). Time-lapse videomicroscopy showing immature DC incubated with CD4+ T cells in the absence of superantigens)
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[img] Other (Video 3 (.avi). Time-lapse videomicroscopy showing immature DC incubated with superantigens and CD4+ T cells)
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[img] Other (Video 4 (.avi). Time-lapse videomicroscopy showing DC exposed to a supernatant collected from co-cultures of DC+ CD4+ T cells+ Superantigens)
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Abstract

Dendritic cells (DCs) control T cell–based immunity. To do so they need to mature and migrate to sites of T-cell priming. We have previously shown that cognate interactions of human CD4+ T cells with DCs induce DC maturation. We show here that CC chemokines produced during antigen-specific T-DC interactions also induce strong morphologic modifications and migration of immature DCs. These modifications are required for efficient T-cell activation. Moreover, we show that CC chemokines produced during antigen-specific DC–T-cell interactions induce the dissolution of structures involved in cell motility and present on immature DCs (ie, podosomes). We thus propose a model in which chemokines secreted during Ag-specific contact between T cells and DCs induce disassembly of interacting and neighboring immature DC podosomes, leading to recruitment of more immature DCs toward sites of antigenic stimulation and to amplification of T-cell responses.


Item Type:Article
Additional Information:Copyright © 2008 by American Society of Hematology. Submitted August 20, 2007; accepted January 8, 2008. Prepublished online as Blood First Edition Paper, January 18, 2008 DOI: 10.1182/blood-2007-08-107755. We thank P. Guermonprez, C. Théry, A.M. Lennon and S. Hugues for critical reading of the manuscript and/or discussion; F. Waharte for assistance with microscopy imaging; and E. Labruyère (Institut Pasteur, Paris) for help with the Dunn Chamber assay. This work was supported by grants from Institut Curie, Inserm, ARC (Association pour la Recherche contre le Cancer). C.N. is a fellow of FRM (Fondation pour la Recherche Medicale). C.N. performed research, analyzed and interpreted data, and drafted the manuscript; M.L., M.T., S.D., and F.M. performed research; K.C. analyzed data; G.O. contributed vital new reagents or analytical tools; S.A. analyzed and interpreted data; and C.H. designed research, analyzed and interpreted data, and drafted the manuscript. Conflict-of-interest disclosure: The authors declare no competing financial interests. The online version of this article contains a data supplement. http://bloodjournal.hematologylibrary.org/cgi/content/full/blood-2007-08-107755/DC1 The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 USC section 1734.
Issue or Number:7
Record Number:CaltechAUTHORS:NOBblo08
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:NOBblo08
Alternative URL:http://dx.doi.org/10.1182/blood-2007-08-107755
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:10084
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:11 Apr 2008
Last Modified:26 Dec 2012 09:56

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