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The Journal of Immunology, 2001, 166: 868-876.
Copyright © 2001 by The American Association of Immunologists

Mast Cell-Dependent B and T Lymphocyte Activation Is Mediated by the Secretion of Immunologically Active Exosomes1

Dimitris Skokos*, Sophie Le Panse{dagger}, Irène Villa*, Jean-Claude Rousselle{ddagger}, Roger Peronet*, Bernard David*, Abdelkader Namane{ddagger} and Salaheddine Mécheri2,*

* Unité d’Immuno-Allergie, Institut Pasteur, Paris, France; {dagger} Institut Jacques Monod, Unité Mixte de Recherche 7592, Paris, France; and {ddagger} Laboratoire de Chimie Structurale des Macromolécules (Unité de Recherche Associeé 2185, Centre National de la Recherche Scientifique), Paris, France

Mitogenic activity of bone marrow-derived mouse mast cells and mast cell lines P815 and MC/9 on B and T lymphocytes is present in their culture supernatants. To identify this activity, mast cells were incubated in serum-free medium and the supernatant was subjected to differential centrifugation, which resulted in two fractions, the hypodense and dense fraction (pellet). When analyzed for their mitogenic activity on spleen cells, all activity was found to be associated with the dense fraction. Electron microscopy studies revealed the presence in this fraction of small vesicles called exosomes with a heterogeneous size from 60 to 100 nm of diameter. When cocultured with spleen cells, purified exosomes induced blast formation, proliferation, as well as IL-2 and IFN-{gamma} production, but no detectable IL-4. Similar data were obtained by injecting exosomes into naive mice. In contrast to mast cell lines, a pretreatment with IL-4 is required for bone marrow-derived mast cells to secrete active exosomes. Structurally, exosomes were found to harbor immunologically relevant molecules such as MHC class II, CD86, LFA-1, and ICAM-1. These findings indicate that mast cells can represent a critical component of the immunoregulatory network through secreted exosomes that display mitogenic activity on B and T lymphocytes both in vitro and in vivo.




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