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

Nature Immunology volume 3, pages 1156–1162 (2002)Cite this article

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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Figure 1: Exosomes from male BMDCs induce activation of Marilyn T cells in vivo and in vitro.
Figure 2: Exosomes produced by H-Y peptide–pulsed D1 cells induce early activation markers on Marilyn T cells in vivo.
Figure 3: H-Y–exosomes induce up-regulation of late activation markers and proliferation of Marilyn T cells in vivo.
Figure 4: Marilyn T cell stimulation by H-Y–exosomes in vitro requires the presence of DCs and MHC molecules on exosomes.
Figure 5: Only DCs can efficiently stimulate Marilyn T cells with H-Y peptide or H-Y–exosomes.
Figure 6: CD8α− DCs are more efficient than CD8α+ DCs in stimulating Marilyn T cells with H-Y peptide or H-Y–exosomes.
Figure 7: H-Y–I-Ab complexes harbored by H-Y–exosomes and CD80 and CD86 costimulatory molecules present on recipient DCs are necessary to induce Marilyn T cell proliferation in vitro.

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

Authors and 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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  1. Clotilde Théry
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Correspondence to Sebastian Amigorena.

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

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Théry, C., Duban, L., Segura, E. et al. Indirect activation of naïve CD4+ T cells by dendritic cell–derived exosomes. Nat Immunol 3, 1156–1162 (2002). https://doi.org/10.1038/ni854

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