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Exosomes: composition, biogenesis and function

Key Points

  • Exosomes are saucer-shaped vesicles of 30–100 nm in diameter, which are delimited by a lipid bi-layer and which float at a density of 1.13–1.19 g ml−1 in sucrose gradients. These vesicles are secreted by various cells in culture.

  • Analysis of the protein composition of exosomes that are secreted by various cells reveals the presence of some common proteins, which define exosomes as a bona fide secreted subcellular compartment, as well as the presence of some cell-type-specific proteins, which could mediate the different functions of exosomes that are produced by different cell types.

  • All of the proteins that have been identified in exosomes are localized in the cell cytosol or endosomal compartments, never in the endoplasmic reticulum, Golgi apparatus, mitochondria or nucleus. Exosomes also contain some plasma-membrane proteins, which have been described also in endosomal compartments. These observations are consistent with the proposed origin of exosomes as internal vesicles of late multivesicular compartments.

  • Formation of the internal vesicles of multivesicular bodies by inward budding from the limiting membrane involves a budding event of inverse membrane orientation compared with the classical intracellular budding events that take place in a cell. All inverse budding events seem to be correlated with an inversion of the transmembrane partition of the lipid phosphatidylserine.

  • Membrane exchanges between cells have been described during the interactions of T cells and antigen-presenting cells (from the T cell to the antigen-presenting cell, or reciprocally, depending on the analyses), or between dendritic cells. It is not clear whether such exchanges involve exosomes.

  • The biological functions of exosomes remain unclear. The original role of exosomes was most probably to eliminate undegraded endosomal or lysosomal proteins and membranes. Recent results indicate, however, that in different cell types, exosomes might have other functions, such as the stimulation or inactivation of T cells, or the transfer of antigens to dendritic cells.

  • Regardless of their putative physiological functions, exosomes have been used successfully in preclinical mouse and human tumour immunotherapy assays. A Phase I clinical trial in melanoma patients is ongoing.


Exosomes are small membrane vesicles of endocytic origin that are secreted by most cells in culture. Interest in exosomes has intensified after their recent description in antigen-presenting cells and the observation that they can stimulate immune responses in vivo. In the past few years, several groups have reported the secretion of exosomes by various cell types, and have discussed their potential biological functions. Here, we describe the physical properties that define exosomes as a specific population of secreted vesicles, we summarize their biological effects, particularly on the immune system, and we discuss the potential roles that secreted vesicles could have as intercellular messengers.

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Figure 1: Summary of the observations that led to the first description of exosomes.
Figure 2: Schematic representation of exosomes produced by dendritic cells.
Figure 3: Orientation of various budding events occuring in a cell.
Figure 4: Working model for the role of exosomes in immune responses.


  1. 1

    Trams, E. G., Lauter, C. J., Salem, N. Jr & Heine, U. Exfoliation of membrane ecto-enzymes in the form of micro-vesicles. Biochim. Biophys. Acta 645, 63–70 (1981).

    CAS  Article  Google Scholar 

  2. 2

    Pan, B. T., Teng, K., Wu, C., Adam, M. & Johnstone, R. M. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J. Cell Biol. 101, 942–948 (1985).

    CAS  Article  Google Scholar 

  3. 3

    Harding, C., Heuser, J. & Stahl, P. Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J. Cell Biol. 97, 329–339 (1983).References 2 and 3 describe very detailed and careful electron-microscopy analyses of the fate of an endocytosed protein in reticulocytes, and point out, for the first time, the possible secretion of the content of multivesicular late endosomes into the extracellular space.

    CAS  Article  Google Scholar 

  4. 4

    Johnstone, R. M., Adam, M., Hammond, J. R., Orr, L. & Turbide, C. Vesicle formation during reticulocyte maturation. Association of plasma-membrane activities with released vesicles (exosomes). J. Biol. Chem. 262, 9412–9420 (1987).

    CAS  PubMed  Google Scholar 

  5. 5

    Peters, P. J. et al. Molecules relevant for T-cell–target-cell interaction are present in cytolytic granules of human T lymphocytes. Eur. J. Immunol. 19, 1469–1475 (1989).

    CAS  Article  Google Scholar 

  6. 6

    Raposo, G. et al. B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 183, 1161–1172 (1996).This study shows, for the first time, the secretion of vesicles that are derived from multivesicular late endosomes by an antigen-presenting cell, and the presence of functional MHC class II molecules on the released exosomes.

    CAS  Article  Google Scholar 

  7. 7

    Raposo, G. et al. Accumulation of major histocompatibility complex class II molecules in mast-cell secretory granules and their release upon degranulation. Mol. Biol. Cell 8, 2631–2645 (1997).

    CAS  Article  Google Scholar 

  8. 8

    Zitvogel, L. et al. Eradication of established murine tumors using a novel cell-free vaccine: dendritic-cell-derived exosomes. Nature Med. 4, 594–600 (1998).This study shows that exosomes can be secreted by dendritic cells, and that such exosomes can induce antigen-dependent T-cell-mediated immune responses in mice.

    CAS  Article  Google Scholar 

  9. 9

    Thery, C. et al. Molecular characterization of dendritic-cell-derived exosomes. Selective accumulation of the heat-shock protein hsc73. J. Cell Biol. 147, 599–610 (1999).

    CAS  Article  Google Scholar 

  10. 10

    Heijnen, H. F., Schiel, A. E., Fijnheer, R., Geuze, H. J. & Sixma, J. J. Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and α-granules. Blood 94, 3791–3799 (1999).

    CAS  PubMed  Google Scholar 

  11. 11

    Davis, J. Q., Dansereau, D., Johnstone, R. M. & Bennett, V. Selective externalization of an ATP-binding protein structurally related to the clathrin-uncoating ATPase/heat-shock protein in vesicles containing terminal transferrin receptors during reticulocyte maturation. J. Biol. Chem. 261, 15368–15371 (1986).

    CAS  PubMed  Google Scholar 

  12. 12

    Thery, C. et al. Proteomic analysis of dendritic-cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J. Immunol. 166, 7309–7318 (2001).A detailed analysis, together with reference 9 , of the protein composition of dendritic-cell-derived exosomes, and a demonstration that they are distinct from apoptotic-cell-derived microvesicles.

    CAS  Article  Google Scholar 

  13. 13

    Skokos, D. et al. Mast-cell-dependent B- and T-lymphocyte activation is mediated by the secretion of immunologically active exosomes. J. Immunol. 166, 868–876 (2001).

    CAS  Article  Google Scholar 

  14. 14

    Martinez-Lorenzo, M. J. et al. Activated human T cells release bioactive Fas ligand and APO2 ligand in microvesicles. J. Immunol. 163, 1274–1281 (1999).

    CAS  Google Scholar 

  15. 15

    Blanchard, N. et al. TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/ζ complex. J. Immunol. 168, 3235–3241 (2002).

    CAS  Article  Google Scholar 

  16. 16

    Wolfers, J. et al. Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nature Med. 7, 297–303 (2001).

    CAS  Article  Google Scholar 

  17. 17

    van Niel, G. et al. Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology 121, 337–349 (2001).

    CAS  Article  Google Scholar 

  18. 18

    Nilsson, B. O., Lennartsson, L., Carlsson, L., Nilsson, S. & Ronquist, G. Expression of prostasome-like granules by the prostate cancer cell lines PC3, Du145 and LnCaP grown in monolayer. Ups. J. Med. Sci. 104, 199–206 (1999).

    CAS  Article  Google Scholar 

  19. 19

    Hess, C., Sadallah, S., Hefti, A., Landmann, R. & Schifferli, J. A. Ectosomes released by human neutrophils are specialized functional units. J. Immunol. 163, 4564–4573 (1999).

    CAS  PubMed  Google Scholar 

  20. 20

    Mack, M. et al. Transfer of the chemokine receptor CCR5 between cells by membrane-derived microparticles: a mechanism for cellular human immunodeficiency virus 1 infection. Nature Med. 6, 769–775 (2000).

    CAS  Article  Google Scholar 

  21. 21

    MacKenzie, A. et al. Rapid secretion of interleukin-1β by microvesicle shedding. Immunity 15, 825–835 (2001).

    CAS  Article  Google Scholar 

  22. 22

    Escola, J. M. et al. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B lymphocytes. J. Biol. Chem. 273, 20121–20127 (1998).

    CAS  Article  Google Scholar 

  23. 23

    Rabesandratana, H., Toutant, J. P., Reggio, H. & Vidal, M. Decay-accelerating factor (CD55) and membrane inhibitor of reactive lysis (CD59) are released within exosomes during in vitro maturation of reticulocytes. Blood 91, 2573–2580 (1998).

    CAS  PubMed  Google Scholar 

  24. 24

    Clayton, A. et al. Analysis of antigen-presenting-cell-derived exosomes, based on immuno-magnetic isolation and flow cytometry. J. Immunol. Methods 247, 163–174 (2001).

    CAS  Article  Google Scholar 

  25. 25

    Srivastava, P. Interaction of heat-shock proteins with peptides and antigen-presenting cells: chaperoning of the innate and adaptive immune responses. Annu. Rev. Immunol. 20, 395–425 (2002).

    CAS  Article  Google Scholar 

  26. 26

    Stubbs, J. D. et al. cDNA cloning of a mouse mammary epithelial cell surface protein reveals the existence of epidermal growth factor-like domains linked to factor VIII-like sequences. Proc. Natl Acad. Sci. USA 87, 8417–8421 (1990).

    CAS  Article  Google Scholar 

  27. 27

    Denzer, K. et al. Follicular dendritic cells carry MHC class-II-expressing microvesicles at their surface. J. Immunol. 165, 1259–1265 (2000).The first direct observation of exosomes in a human tissue (tonsils) in the absence of any in vitro culture step. Most of the other data in this paper, however, are obtained after the in vitro culture of B cells.

    CAS  Article  Google Scholar 

  28. 28

    Mobius, W. et al. Immunoelectron microscopic localization of cholesterol using biotinylated and non-cytolytic perfringolysin O. J. Histochem. Cytochem. 50, 43–55 (2002).

    CAS  Article  Google Scholar 

  29. 29

    Gruenberg, J. & Maxfield, F. R. Membrane transport in the endocytic pathway. Curr. Opin. Cell Biol. 7, 552–563 (1995).

    CAS  Article  Google Scholar 

  30. 30

    Babst, M., Odorizzi, G., Estepa, E. J. & Emr, S. D. Mammalian tumor susceptibility gene 101 (TSG101) and the yeast homologue, Vps23p, both function in late endosomal trafficking. Traffic 1, 248–258 (2000).

    CAS  Article  Google Scholar 

  31. 31

    Vincent-Schneider, H. et al. Exosomes bearing HLA–DR1 molecules need dendritic cells to efficiently stimulate specific T cells. Int. Immunol. 14, 713–722 (2002).

    CAS  Article  Google Scholar 

  32. 32

    Katzmann, D. J., Babst, M. & Emr, S. D. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell 106, 145–155 (2001).

    CAS  Article  Google Scholar 

  33. 33

    Hicke, L. A new ticket for entry into budding vesicles — ubiquitin. Cell 106, 527–530 (2001).

    CAS  Article  Google Scholar 

  34. 34

    Reggiori, F. & Pelham, H. R. Sorting of proteins into multivesicular bodies: ubiquitin-dependent and -independent targeting. EMBO J. 20, 5176–5186 (2001).

    CAS  Article  Google Scholar 

  35. 35

    Aupeix, K. et al. The significance of shed membrane particles during programmed cell death in vitro, and in vivo, in HIV-1 infection. J. Clin. Invest. 99, 1546–1554 (1997).

    CAS  Article  Google Scholar 

  36. 36

    Mather, I. H. in The Mammary Gland (eds Neville, M. C. & Daniel, C. W.) 217–267 (Plenum, New York, 1987).

    Book  Google Scholar 

  37. 37

    Peterson, J. A., Patton, S. & Hamosh, M. Glycoproteins of the human milk fat globule in the protection of the breast-fed infant against infections. Biol. Neonate 74, 143–162 (1998).

    CAS  Article  Google Scholar 

  38. 38

    Garrus, J. E. et al. Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell 107, 55–65 (2001).

    CAS  Article  Google Scholar 

  39. 39

    VerPlank, L. et al. Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L domain in HIV type 1 Pr55(Gag). Proc. Natl Acad. Sci. USA 98, 7724–7729 (2001).

    CAS  Article  Google Scholar 

  40. 40

    Martin-Serrano, J., Zang, T. & Bieniasz, P. D. HIV-1 and Ebola virus encode small peptide motifs that recruit Tsg101 to sites of particle assembly to facilitate egress. Nature Med. 7, 1313–1319 (2001).

    CAS  Article  Google Scholar 

  41. 41

    Blott, E. J. & Griffiths, G. M. Secretory lysosomes. Nature Rev. Mol. Cell Biol. 3, 122–131 (2002).

    CAS  Article  Google Scholar 

  42. 42

    Pelham, H. R. SNAREs and the specificity of membrane fusion. Trends Cell Biol. 11, 99–101 (2001).

    CAS  Article  Google Scholar 

  43. 43

    Paumet, F. et al. Soluble NSF attachment protein receptors (SNAREs) in RBL-2H3 mast cells: functional role of syntaxin 4 in exocytosis and identification of a vesicle-associated membrane protein-8-containing secretory compartment. J. Immunol. 164, 5850–5857 (2000).

    CAS  Article  Google Scholar 

  44. 44

    Hibi, T., Hirashima, N. & Nakanishi, M. Rat basophilic leukemia cells express syntaxin-3 and VAMP-7 in granule membranes. Biochem. Biophys. Res. Commun. 271, 36–41 (2000).

    CAS  Article  Google Scholar 

  45. 45

    Guo, Z., Turner, C. & Castle, D. Relocation of the t-SNARE SNAP-23 from lamellipodia-like cell-surface projections regulates compound exocytosis in mast cells. Cell 94, 537–548 (1998).

    CAS  Article  Google Scholar 

  46. 46

    Martinez, I. et al. Synaptotagmin VII regulates Ca2+-dependent exocytosis of lysosomes in fibroblasts. J. Cell Biol. 148, 1141–1149 (2000).

    CAS  Article  Google Scholar 

  47. 47

    Baram, D. et al. Synaptotagmin II negatively regulates Ca2+-triggered exocytosis of lysosomes in mast cells. J. Exp. Med. 189, 1649–1658 (1999).

    CAS  Article  Google Scholar 

  48. 48

    Hwang, I. et al. T cells can use either T-cell receptor or CD28 receptors to absorb and internalize cell-surface molecules derived from antigen-presenting cells. J. Exp. Med. 191, 1137–1148 (2000).

    CAS  Article  Google Scholar 

  49. 49

    Huang, J. F. et al. TCR-mediated internalization of peptide–MHC complexes acquired by T cells. Science 286, 952–954 (1999).

    CAS  Article  Google Scholar 

  50. 50

    Hudrisier, D., Riond, J., Mazarguil, H., Gairin, J. E. & Joly, E. Cutting edge: CTLs rapidly capture membrane fragments from target cells in a TCR signaling-dependent manner. J. Immunol. 166, 3645–3649 (2001).

    CAS  Article  Google Scholar 

  51. 51

    Stinchcombe, J. C., Bossi, G., Booth, S. & Griffiths, G. M. The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity 15, 751–761 (2001).

    CAS  Article  Google Scholar 

  52. 52

    Brezinschek, R. I., Oppenheimer-Marks, N. & Lipsky, P. E. Activated T cells acquire endothelial cell-surface determinants during transendothelial migration. J. Immunol. 162, 1677–1684 (1999).

    CAS  PubMed  Google Scholar 

  53. 53

    Russo, V. et al. Acquisition of intact allogeneic human leukocyte antigen molecules by human dendritic cells. Blood 95, 3473–3477 (2000).

    CAS  PubMed  Google Scholar 

  54. 54

    Batista, F. D., Iber, D. & Neuberger, M. S. B cells acquire antigen from target cells after synapse formation. Nature 411, 489–494 (2001).

    CAS  Article  Google Scholar 

  55. 55

    Patel, D. M., Arnold, P. Y., White, G. A., Nardella, J. P. & Mannie, M. D. Class II MHC/peptide complexes are released from APC and are acquired by T-cell responders during specific antigen recognition. J. Immunol. 163, 5201–5210 (1999).

    CAS  PubMed  Google Scholar 

  56. 56

    Arnold, P. Y. & Mannie, M. D. Vesicles bearing MHC class II molecules mediate transfer of antigen from antigen-presenting cells to CD4+ T cells. Eur. J. Immunol. 29, 1363–1373 (1999).

    CAS  Article  Google Scholar 

  57. 57

    Bedford, P., Garner, K. & Knight, S. C. MHC class II molecules transferred between allogeneic dendritic cells stimulate primary mixed leukocyte reactions. Int. Immunol. 11, 1739–1744 (1999).

    CAS  Article  Google Scholar 

  58. 58

    Knight, S. C., Iqball, S., Roberts, M. S., Macatonia, S. & Bedford, P. A. Transfer of antigen between dendritic cells in the stimulation of primary T-cell proliferation. Eur. J. Immunol. 28, 1636–1644 (1998).

    CAS  Article  Google Scholar 

  59. 59

    Sharrow, S. O., Mathieson, B. J. & Singer, A. Cell-surface appearance of unexpected host MHC determinants on thymocytes from radiation bone-marrow chimeras. J. Immunol. 126, 1327–1335 (1981).

    CAS  PubMed  Google Scholar 

  60. 60

    Gray, D., Kosco, M. & Stockinger, B. Novel pathways of antigen presentation for the maintenance of memory. Int. Immunol. 3, 141–148 (1991).

    CAS  Article  Google Scholar 

  61. 61

    Greco, V., Hannus, M. & Eaton, S. Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell 106, 633–645 (2001).This study shows a visualization in vivo in embryonic tissues of the transfer of membrane structures that are labelled with a fluorescent lipid between adjacent cells. The membrane structures that are involved have not been characterized.

    CAS  Article  Google Scholar 

  62. 62

    Pan, B. T. & Johnstone, R. M. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell 33, 967–978 (1983).

    CAS  Article  Google Scholar 

  63. 63

    Karlsson, M. et al. 'Tolerosomes' are produced by intestinal epithelial cells. Eur. J. Immunol. 31, 2892–2900 (2001).

    CAS  Article  Google Scholar 

  64. 64

    Dukers, D. F. et al. Direct immunosuppressive effects of EBV-encoded latent membrane protein 1. J. Immunol. 165, 663–670 (2000).

    CAS  Article  Google Scholar 

  65. 65

    Monleon, I. et al. Differential secretion of Fas ligand- or APO2 ligand/TNF-related apoptosis-inducing ligand-carrying microvesicles during activation-induced death of human T cells. J. Immunol. 167, 6736–6744 (2001).

    CAS  Article  Google Scholar 

  66. 66

    Andreola, G. et al. Induction of lymphocyte apoptosis by tumor-cell secretion of FasL-bearing microvesicles. J. Exp. Med. 195, 1303–1316 (2002).

    CAS  Article  Google Scholar 

  67. 67

    André, F. et al. Malignant ascitis accumulate immunogenic tumor-derived exosomes: novel approach for cancer immunotherapy. Lancet (in the press).

  68. 68

    Kleijmeer, M. J. et al. Antigen loading of MHC class I molecules in the endocytic tract. Traffic 2, 124–137 (2001).

    CAS  Article  Google Scholar 

  69. 69

    Rieu, S., Geminard, C., Rabesandratana, H., Sainte-Marie, J. & Vidal, M. Exosomes released during reticulocyte maturation bind to fibronectin via integrin α4β1. Eur. J. Biochem. 267, 583–590 (2000).

    CAS  Article  Google Scholar 

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We thank C. Hivroz and P. Benaroch for helpful comments on the manuscript. S.A. and L.Z. were supported by European Community grants.

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Correspondence to Clotilde Théry.

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annexin I

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annexin V

annexin VI












































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A family of cytosolic proteins that have phospholipid-binding domains, the association of which with intracellular membranes is regulated by Ca2+. Several annexins are involved in membrane-fusion events between intracellular compartments.


Cytosolic proteins that have GTPase activity, which, in their GTP-bound form, associate with membranes. Different RAB proteins associate with different intracellular compartments — for example, RAB5 associates with early endosomes, RAB7 with late endosomes and RAB11 with recycling endosomes.


(HSPs). A family of proteins that are involved in the binding of other misfolded proteins, and transporting them to the cellular degradation machinery. Several HSPs are synthesized only in conditions of stress, such as heat shock, but a few family members — such as endoplasmic-reticulum-resident gp96, and cytosolic HSC70 and HSP84 — are expressed constitutively.


A family of transmembrane proteins that have four transmembrane domains and two extracellular domains of different sizes, which are defined by several conserved amino acids in the transmembrane domains. Their function is not known clearly, but they seem to interact with many other transmembrane proteins and to form large multimeric protein networks.


In mastocytes and cytotoxic T lymphocytes, this term refers to the activation-induced fusion of secretory granules with the plasma membrane, and to the subsequent release of the content of these granules into the extracellular space.


(FDCs). Cells with a dendritic morphology that are present in the lymph nodes, where they present intact antigens held in immune complexes to B cells. FDCs are of non-haematopoietic origin, and are not related to dendritic cells.


This term refers to the ability of certain antigen-presenting cells (APCs) to load peptides that are derived from exogenous antigens onto MHC class I molecules. This property is atypical, as most cells present exclusively peptides from their endogenous proteins on MHC class I molecules. Cross-presentation is essential for the initiation of immune responses against viruses that do not infect APCs.

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Théry, C., Zitvogel, L. & Amigorena, S. Exosomes: composition, biogenesis and function. Nat Rev Immunol 2, 569–579 (2002).

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