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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.
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IMMUNOBIOLOGY
ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming
Elodie Segura,
Carole Nicco,
Bérangère Lombard,
Philippe Véron,
Graça Raposo,
Frédéric Batteux,
Sebastian Amigorena, and
Clotilde Théry
From Institut National de la Santé et de la Recherche Médicale (INSERM) U653, the Laboratory of Mass Spectrometry and Proteomics, Centre National de la Recherche ScientifiqueUnité Mixte de Recherche (CNRS UMR) 144, Institut Curie; and the Laboratoire d'immunologie, Faculté et Hôpital Cochin, Université Paris V, Paris, France.
Exosomes are secreted vesicles formed in late endocytic compartments. Immature dendritic cells (DCs) secrete exosomes, which transfer functional major histocompatibility complex (MHC)peptide complexes to other DCs. Since immature and mature DCs induce different functional T-cell responses (ie, tolerance versus priming), we asked whether DC maturation also influenced the priming abilities of their exosomes. We show that exosomes secreted by lipopolysaccharide (LPS)treated mature DCs are 50- to 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, intercellular adhesion molecule 1 (ICAM-1), and bear little milk-fat globuleepidermal growth factorfactor VIII (MFG-E8) as compared with 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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