ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming.
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 globule-epidermal growth factor-factor 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.
Segura
Elodie
E
Institut National de la Santé et de la Recherche Médicale, Laboratory of Mass Spectrometry and Proteomics, Centre National de la Recherche Scientifique-Unité Mixte de Recherche, Paris, France.
Nicco
Carole
C
Lombard
Bérangère
B
Véron
Philippe
P
Raposo
Graça
G
Batteux
Frédéric
F
Amigorena
Sebastian
S
Théry
Clotilde
C
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008854:Microscopy, Electron; D008894:Milk Proteins / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D022142:Secretory Vesicles / Q000276:immunology* / Q000378:metabolism / Q000648:ultrastructure
D015703:Antigens, CD; D000954:Antigens, Surface; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C490919:Mfge8 protein, mouse; D008894:Milk Proteins; D018799:Intercellular Adhesion Molecule-1