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Blood, 1 July 2005, Vol. 106, No. 1, pp. 216-223.
Prepublished online as a Blood First Edition Paper on March 24, 2005; DOI 10.1182/blood-2005-01-0220.
Previous Article | Next Article 
Submitted January 18, 2005
Accepted March 10, 2005
ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T cell priming
Elodie Segura, Carole Nicco, Berangere Lombard, Philippe Veron, Graca Raposo, Frederic Batteux, Sebastian Amigorena, and Clotilde Thery*
INSERM U653, Institut Curie, Paris, France
Laboratoire d'Immunologie, UPRES1833, Faculte et Hopital Cochin, Universite Paris V, Paris, France
Laboratory of Mass Spectrometry and Proteomics, Institut Curie, Paris, France
CNRS UMR 144, Institut Curie, Paris, France
* Corresponding author; email: clotilde.thery{at}curie.fr.
Exosomes are secreted vesicles formed in late endocytic compartments. Immature dendritic cells (DCs) secrete exosomes which transfer functional MHC-peptide complexes to other DCs. Since immature and mature DCs induce different functional T cell responses (i.e. tolerance versus priming), we asked whether DC maturation also influenced the priming abilities of their exosomes. We show that exosomes secreted by LPS-treated mature DCs are 50-100 fold more potent to induce antigen-specific T cell activation in vitro than exosomes from immature DCs. In vitro, exosomes from mature DCs transfer to B lymphocytes the ability to prime naive T cells. In vivo, only mature exosomes trigger effector T cell responses, leading to fast skin graft rejection. Proteomic and biochemical analyses revealed that mature exosomes are enriched in MHC class II, B7.2, ICAM-1, and bear little MFG-E8 as compared to immature exosomes. Functional analysis using DC-derived exosomes from knock-out mice showed that MHC class II and ICAM-1 are required for mature exosomes to prime naive T cells, whereas B7.2 and MFG-E8 are dispensable. Therefore, changes in protein composition and priming abilities of exosomes reflect the maturation signals received by DCs.

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