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Indirect activation of naïve CD4+ T cells by dendritic cell–derived exosomes

Nature Immunologyvolume 3pages11561162 (2002) | Download Citation

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Abstract

Dendritic cells (DCs) secrete vesicles of endosomal origin, called exosomes, that bear major histocompatibility complex (MHC) and T cell costimulatory molecules. Here, we found that injection of antigen- or peptide-bearing exosomes induced antigen-specific naïve CD4+ T cell activation in vivo. In vitro, exosomes did not induce antigen-dependent T cell stimulation unless mature CD8α DCs were also present in the cultures. These mature DCs could be MHC class II–negative, but had to bear CD80 and CD86. Therefore, in addition to carrying antigen, exosomes promote the exchange of functional peptide-MHC complexes between DCs. Such a mechanism may increase the number of DCs bearing a particular peptide, thus amplifying the initiation of primary adaptive immune responses.

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Acknowledgements

We thank Z. Maciorowski for help with cell sorting, C. Hivroz and A. Sarukhan for critical reading of the manuscript, G. Raposo and L. Zitvogel for helpful discussions and P. Ricciardi-Castagnoli for the D1 cell line. Supported by Institut Curie, INSERM and Anosys Inc. with grants from Association pour la Recherche sur le Cancer (grant number 5913), Ministère de la Recherche (ACI number 4219) and European Community (grant number QoL-2001-00093).

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Author notes

  1. Clotilde Théry, Livine Duban, Olivier Lantz and Sebastian Amigorena: These authors contributed equally to this work.

Affiliations

  1. INSERM U520, Institut Curie, 12 rue Lhomond, Paris, 75005, France

    • Clotilde Théry
    • , Livine Duban
    • , Elodie Segura
    • , Philippe Véron
    • , Olivier Lantz
    •  & Sebastian Amigorena
  2. Laboratoire d'Immunologie Préclinique, Institut Curie, 26 rue d'Ulm, Paris, 75005, France

    • Livine Duban
    •  & Olivier Lantz

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Competing interests

S. A. is a consultant for and shareholder of the company ANOSYS, which is developing the use of exosomes for immunotherapy.

Corresponding author

Correspondence to Sebastian Amigorena.

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https://doi.org/10.1038/ni854

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