1932

Abstract

The initiation and maintenance of adaptive immunity require multifaceted modes of communication between different types of immune cells, including direct intercellular contact, secreted soluble signaling molecules, and extracellular vesicles (EVs). EVs can be formed as microvesicles directly pinched off from the plasma membrane or as exosomes secreted by multivesicular endosomes. Membrane receptors guide EVs to specific target cells, allowing directional transfer of specific and complex signaling cues. EVs are released by most, if not all, immune cells. Depending on the type and status of their originating cell, EVs may facilitate the initiation, expansion, maintenance, or silencing of adaptive immune responses. This review focusses on EVs from professional antigen-presenting cells, their demonstrated and speculated roles, and their potential for cancer immunotherapy.

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2018-04-26
2024-03-28
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Literature Cited

  1. Raposo G, Stoorvogel W. 1.  2013. Extracellular vesicles: exosomes, microvesicles, and friends. J. Cell Biol. 200:4373–83 [Google Scholar]
  2. Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV. 2.  et al. 1996. B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 183:1161–72 [Google Scholar]
  3. Théry C, Duban L, Segura E, Véron P, Lantz O, Amigorena S. 3.  2002. Indirect activation of naïve CD4+ T cells by dendritic cell-derived exosomes. Nat. Immunol. 3:121156–62 [Google Scholar]
  4. Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C. 4.  et al. 1998. Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat. Med. 4:594–600 [Google Scholar]
  5. Mittelbrunn M, Gutiérrez-Vázquez C, Villarroya-Beltri C, González S, Sánchez-Cabo F. 5.  et al. 2011. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat. Commun. 2:282 [Google Scholar]
  6. Van der Vlist EJ, Nolte-’t Hoen ENM, Stoorvogel W, Arkesteijn GJA, Wauben MHM. 6.  2012. Fluorescent labeling of nano-sized vesicles released by cells and subsequent quantitative and qualitative analysis by high-resolution flow cytometry. Nat. Protoc. 7:71311–26 [Google Scholar]
  7. Chevillet JR, Kang Q, Ruf IK, Briggs HA, Vojtech LN. 7.  et al. 2014. Quantitative and stoichiometric analysis of the microRNA content of exosomes. PNAS 111:4114888–93 [Google Scholar]
  8. Gutiérrez-Vázquez C, Villarroya-Beltri C, Mittelbrunn M, Sánchez-Madrid F. 8.  2013. Transfer of extracellular vesicles during immune cell-cell interactions. Immunol. Rev. 251:125–42 [Google Scholar]
  9. Kowal J, Arras G, Colombo M, Morath JP. 9.  et al. 2016. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. PNAS 113:E968–77 [Google Scholar]
  10. Stoorvogel W. 10.  2015. Resolving sorting mechanisms into exosomes. Cell Res 25:5531–32 [Google Scholar]
  11. Colombo M, Raposo G, Théry C. 11.  2014. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu. Rev. Cell Dev. Biol. 30:255–89 [Google Scholar]
  12. Théry C, Ostrowski M, Segura E. 12.  2009. Membrane vesicles as conveyors of immune responses. Nat. Rev. Immunol. 9:8581–93 [Google Scholar]
  13. Robbins PD, Morelli AE. 13.  2014. Regulation of immune responses by extracellular vesicles. Nat. Rev. Immunol. 14:3195–208 [Google Scholar]
  14. Lorber MI, Loken MR, Stall AM, Fitch FW. 14.  1982. I-A antigens on cloned alloreactive murine T lymphocytes are acquired passively. J. Immunol. 128:62798–803 [Google Scholar]
  15. Nepom JT, Benacerraf B, Germain RN. 15.  1981. Acquisition of syngeneic I-A determinants by T cells proliferating in response to poly (Glu60Ala30Tyr10). J. Immunol. 127:3888–92 [Google Scholar]
  16. Sharrow SO, Mathieson BJ, Singer A. 16.  1981. Cell surface appearance of unexpected host MHC determinants on thymocytes from radiation bone marrow chimeras. J. Immunol. 126:1327–35 [Google Scholar]
  17. Norbury CC. 17.  2016. Defining cross presentation for a wider audience. Curr. Opin. Immunol. 40:110–16 [Google Scholar]
  18. Dolan BP, Gibbs KD, Ostrand-Rosenberg S. 18.  2006. Dendritic cells cross-dressed with peptide MHC class I complexes prime CD8+ T cells. J. Immunol. 177:6018–24 [Google Scholar]
  19. Wakim LM, Bevan MJ. 19.  2011. Cross-dressed dendritic cells drive memory CD8+ T-cell activation after viral infection. Nature 471:7340629–32 [Google Scholar]
  20. Herrera OB, Golshayan D, Tibbott R, Ochoa FS, James MJ. 20.  et al. 2004. A novel pathway of alloantigen presentation by dendritic cells. J. Immunol. 173:4828–37 [Google Scholar]
  21. Qureshi OS, Zheng Y, Nakamura K, Attridge K, Manzotti C. 21.  et al. 2011. Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4. Science 3322011:600–3 [Google Scholar]
  22. He T, Tang C, Liu Y, Ye Z, Wu X. 22.  et al. 2007. Bidirectional membrane molecule transfer between dendritic and T cells. Biochem. Biophys. Res. Commun. 359:202–8 [Google Scholar]
  23. Onfelt B, Nedvetzki S, Yanagi K, Davis DM. 23.  2004. Cutting edge: membrane nanotubes connect immune cells. J. Immunol. 173:1511–13 [Google Scholar]
  24. Stinchcombe JC, Bossi G, Booth S, Griffiths GM. 24.  2001. The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity 15:751–61 [Google Scholar]
  25. McCoy-Simandle K, Hanna SJ, Cox D. 25.  2015. Exosomes and nanotubes: control of immune cell communication. Int. J. Biochem. Cell Biol. 71:44–54 [Google Scholar]
  26. Schiller C, Huber JE, Diakopoulos KN, Weiss EH. 26.  2013. Tunneling nanotubes enable intercellular transfer of MHC class I molecules. Hum. Immunol. 74:4412–16 [Google Scholar]
  27. Zaccard CR, Watkins SC, Kalinski P, Fecek RJ, Yates AL. 27.  et al. 2014. CD40L induces functional tunneling nanotube networks exclusively in dendritic cells programmed by mediators of type 1 immunity. J. Immunol. 194:1047–56 [Google Scholar]
  28. Allan RS, Waithman J, Bedoui S, Jones CM, Villadangos JA. 28.  et al. 2006. Migratory dendritic cells transfer antigen to a lymph node-resident dendritic cell population for efficient CTL priming. Immunity 25:153–62 [Google Scholar]
  29. Qu C, Nguyen VA, Merad M, Randolph GJ. 29.  2009. MHC class I/peptide transfer between dendritic cells overcomes poor cross-presentation by monocyte-derived APCs that engulf dying cells. J. Immunol. 182:3650–59 [Google Scholar]
  30. Kumar A, Kim JH, Ranjan P, Metcalfe MG, Cao W. 30.  et al. 2017. Influenza virus exploits tunneling nanotubes for cell-to-cell spread. Sci. Rep. 7:40360 [Google Scholar]
  31. Hashimoto M, Bhuyan F, Hiyoshi M, Noyori O, Nasser H. 31.  et al. 2016. Potential role of the formation of tunneling nanotubes in HIV-1 spread in macrophages. J. Immunol. 196:1832–41 [Google Scholar]
  32. Joly E, Hudrisier D. 32.  2003. What is trogocytosis and what is its purpose?. Nat. Immunol. 4:9815 [Google Scholar]
  33. Miyake K, Shiozawa N, Nagao T, Yoshikawa S, Yamanishi Y, Karasuyama H. 33.  2017. Trogocytosis of peptide-MHC class II complexes from dendritic cells confers antigen-presenting ability on basophils. PNAS 114:5201615973 [Google Scholar]
  34. Buschow SI, Nolte-’t Hoen ENM, van Niel G, Pols MS, ten Broeke T. 34.  et al. 2009. MHC II in dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways. Traffic 10:301528–42 [Google Scholar]
  35. Dustin ML. 35.  2014. The immunological synapse. Cancer Immunol. Res. 1:71–75 [Google Scholar]
  36. Wetzel SA, McKeithan TW, Parker DC. 36.  2005. Peptide-specific intercellular transfer of MHC class II to CD4+ T cells directly from the immunological synapse upon cellular dissociation. J. Immunol. 174:80–89 [Google Scholar]
  37. Choudhuri K, Llodrá J, Roth EW, Tsai J, Gordo S. 37.  et al. 2014. Polarized release of T-cell-receptor-enriched microvesicles at the immunological synapse. Nature 507:118–23 [Google Scholar]
  38. Xiang J, Huang H, Liu Y. 38.  2005. A new dynamic model of CD8+ T effector cell responses via CD4+ T helper-antigen-presenting cells. J. Immunol. 174:7497–505 [Google Scholar]
  39. Mittelbrunn M, Vicente-Manzanares M, Sánchez-Madrid F. 39.  2015. Organizing polarized delivery of exosomes at synapses. Traffic 16:327–37 [Google Scholar]
  40. Pulecio J, Petrovic J, Prete F, Chiaruttini G, Lennon-Dumenil A-M. 40.  et al. 2010. Cdc42-mediated MTOC polarization in dendritic cells controls targeted delivery of cytokines at the immune synapse. J. Exp. Med. 207:122719–32 [Google Scholar]
  41. Muntasell A, Berger AC, Roche PA. 41.  2007. T cell-induced secretion of MHC class II-peptide complexes on B cell exosomes. EMBO J 26:194263–72 [Google Scholar]
  42. Nolte-’t Hoen ENM, Buschow SI, Anderton SM, Stoorvogel W, Wauben MHM. 42.  2009. Activated T cells recruit exosomes secreted by dendritic cells via LFA-1. Blood 113:1977–81 [Google Scholar]
  43. Segura E, Amigorena S, Théry C. 43.  2005. Mature dendritic cells secrete exosomes with strong ability to induce antigen-specific effector immune responses. Blood Cells Mol. Dis. 35:89–93 [Google Scholar]
  44. ten Broeke T, van Niel G, Wauben MHM, Wubbolts R, Stoorvogel W. 44.  2011. Endosomally stored MHC class II does not contribute to antigen presentation by dendritic cells at inflammatory conditions. Traffic 12:1025–36 [Google Scholar]
  45. Tamai K, Tanaka N, Nakano T, Kakazu E, Kondo Y. 45.  et al. 2010. Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein. Biochem. Biophys. Res. Commun. 399:3384–90 [Google Scholar]
  46. Colombo M, Moita C, van Niel G, Kowal J, Vigneron J. 46.  et al. 2013. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J. Cell Sci. 126:5553–65 [Google Scholar]
  47. Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G. 47.  et al. 2010. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol. 12:119–30 [Google Scholar]
  48. Qazi KR, Gehrmann U, Domange Jordö E, Karlsson MCI, Gabrielsson S. 48.  2009. Antigen-loaded exosomes alone induce Th1-type memory through a B-cell-dependent mechanism. Blood 113:122673–83 [Google Scholar]
  49. Nolte-’t Hoen ENM, van der Vlist EJ, de Boer-Brouwer M, Arkesteijn GJA, Stoorvogel W, Wauben MHM. 49.  2013. Dynamics of dendritic cell-derived vesicles: high-resolution flow cytometric analysis of extracellular vesicle quantity and quality. J. Leukoc. Biol. 93:395–402 [Google Scholar]
  50. Soo CY, Song Y, Zheng Y, Campbell EC, Riches AC. 50.  et al. 2012. Nanoparticle tracking analysis monitors microvesicle and exosome secretion from immune cells. Immunology 136:192–97 [Google Scholar]
  51. Pizzirani C, Ferrari D, Chiozzi P, Adinolfi E, Sandonà D. 51.  et al. 2007. Stimulation of P2 receptors causes release of IL-1β-loaded microvesicles from human dendritic cells. Blood 109:93856–64 [Google Scholar]
  52. Arraud N, Linares R, Tan S, Gounou C, Pasquet JM. 52.  et al. 2014. Extracellular vesicles from blood plasma: determination of their morphology, size, phenotype and concentration. J. Thromb. Haemost. 12:614–27 [Google Scholar]
  53. Ren Y, Yang J, Xie R, Gao L, Yang Y. 53.  et al. 2011. Exosomal-like vesicles with immune-modulatory features are present in human plasma and can induce CD4+ T-cell apoptosis in vitro. Transfusion 51:1002–11 [Google Scholar]
  54. Morelli AE, Larregina AT, Shufesky WJ, Sullivan MLG, Stolz DB. 54.  et al. 2004. Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood 104:103257–66 [Google Scholar]
  55. Saunderson SC, Dunn AC, Crocker PR, McLellan AD. 55.  2014. CD169 mediates the capture of exosomes in spleen and lymph node. Blood 123:2208–16 [Google Scholar]
  56. Montecalvo A, Shufesky WJ, Stolz DB, Sullivan MG, Wang Z. 56.  et al. 2008. Exosomes as a short-range mechanism to spread alloantigen between dendritic cells during T cell allorecognition. J. Immunol. 180:3081–90 [Google Scholar]
  57. Segura E, Amigorena S. 57.  2015. Cross-presentation in mouse and human dendritic cells. Advances in Immunology 127 F Alt 1–31 Oxford, UK: Elsevier [Google Scholar]
  58. Nair-Gupta P, Baccarini A, Tung N, Seyffer F, Florey O. 58.  et al. 2014. TLR signals induce phagosomal MHC-I delivery from the endosomal recycling compartment to allow cross-presentation. Cell 158:506–21 [Google Scholar]
  59. Streng-Ouwehand I, Ho NI, Litjens M, Kalay H, Boks MA. 59.  et al. 2016. Glycan modification of antigen alters its intracellular routing in dendritic cells, promoting priming of T cells. eLife 5:1–21 [Google Scholar]
  60. Kuwana M. 60.  2002. Induction of anergic and regulatory T cells by plasmacytoid dendritic cells and other dendritic cell subsets. Hum. Immunol. 63:1156–63 [Google Scholar]
  61. Heath WR, Kurts C, Miller JF, Carbone FR. 61.  1998. Cross-tolerance: a pathway for inducing tolerance to peripheral tissue antigens. J. Exp. Med. 187:101549–53 [Google Scholar]
  62. Admyre C, Johansson SM, Paulie S, Gabrielsson S. 62.  2006. Direct exosome stimulation of peripheral human T cells detected by ELISPOT. Eur. J. Immunol. 36:1772–81 [Google Scholar]
  63. André F, Chaput N, Schartz NEC, Flament C, Aubert N. 63.  et al. 2004. Exosomes as potent cell-free peptide-based vaccine: I. Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells. J. Immunol. 172:2126–36 [Google Scholar]
  64. Chaput N, Schartz NEC, André F, Taieb J, Novault S. 64.  et al. 2004. Exosomes as potent cell-free peptide-based vaccine: II. Exosomes in CpG adjuvants efficiently prime naive Tc1 lymphocytes leading to tumor rejection. J. Immunol. 172:2137–46 [Google Scholar]
  65. Utsugi-Kobukai S, Fujimaki H, Hotta C, Nakazawa M, Minami M. 65.  2003. MHC class I-mediated exogenous antigen presentation by exosomes secreted from immature and mature bone marrow derived dendritic cells. Immunol. Lett. 89:125–31 [Google Scholar]
  66. Hao S, Bai O, Li F, Yuan J, Laferte S, Xiang J. 66.  2006. Mature dendritic cells pulsed with exosomes stimulate efficient cytotoxic T-lymphocyte responses and antitumour immunity. Immunology 120:90–102 [Google Scholar]
  67. Münz C. 67.  2012. Antigen processing for MHC class II presentation via autophagy. Front. Immunol. 3:1–6 [Google Scholar]
  68. ten Broeke T, Wubbolts R, Stoorvogel W. 68.  2013. MHC class II antigen presentation by dendritic cells regulated through endosomal sorting. Cold Spring Harb. Perspect. Biol. 5:a016873 [Google Scholar]
  69. Van Niel G, Wubbolts R, ten Broeke T, Buschow SI, Ossendorp FA. 69.  et al. 2006. Dendritic cells regulate exposure of MHC class II at their plasma membrane by oligoubiquitination. Immunity 25:885–94 [Google Scholar]
  70. Steinman RM, Hawiger D, Nussenzweig MC. 70.  2003. Tolerogenic dendritic cells. Annu. Rev. Immunol. 21:685–711 [Google Scholar]
  71. Zou T, Caton AJ, Koretzky GA, Kambayashi T. 71.  2010. Dendritic cells induce regulatory T cell proliferation through antigen-dependent and -independent interactions. J. Immunol. 185:2790–99 [Google Scholar]
  72. Ahrends T, Babala N, Xiao Y, Yagita H, Van Eenennaam H, Borst J. 72.  2016. CD27 agonism plus PD-1 blockade recapitulates CD4+ T-cell help in therapeutic anticancer vaccination. Cancer Res 76:2921–31 [Google Scholar]
  73. Arens R, Loewendorf A, Her MJ, Schneider-Ohrum K, Shellam GR. 73.  et al. 2011. B7-mediated costimulation of CD4 T cells constrains cytomegalovirus persistence. J. Virol. 85:1390–96 [Google Scholar]
  74. Melief CJM, van Hall T, Arens R, Ossendorp F, van der Burg SH. 74.  2015. Therapeutic cancer vaccines. J. Clin. Investig. 125:93401–12 [Google Scholar]
  75. Bedford P, Garner K, Knight S. 75.  1999. MHC class II molecules transferred between allogeneic dendritic cells stimulate primary mixed lymphocyte reactions. Int. Immunol. 11:1739–44 [Google Scholar]
  76. de Heusch M, Blocklet D, Egrise D, Hauquier B, Vermeersch M. 76.  et al. 2007. Bidirectional MHC molecule exchange between migratory and resident dendritic cells. J. Leukoc. Biol. 82:861–68 [Google Scholar]
  77. Segura E, Nicco C, Lombard B, Veron P, Raposo G. 77.  et al. 2005. ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T cell priming. Blood 106:1216–23 [Google Scholar]
  78. Segura E, Guérin C, Hogg N, Amigorena S, Théry C. 78.  2007. CD8+ dendritic cells use LFA-1 to capture MHC-peptide complexes from exosomes in vivo. J. Immunol. 179:1489–96 [Google Scholar]
  79. Vincent-Schneider H, Stumptner-Cuvelette P, Lankar D, Pain S, Raposo G. 79.  et al. 2002. Exosomes bearing HLA-DR1 molecules need dendritic cells to efficiently stimulate specific T cells. Int. Immunol. 7:713–22 [Google Scholar]
  80. Schnitzer JK, Berzel S, Fajardo-Moser M, Remer KA, Moll H. 80.  2010. Fragments of antigen-loaded dendritic cells (DC) and DC-derived exosomes induce protective immunity against Leishmania major.. Vaccine 28:365785–93 [Google Scholar]
  81. Colino J, Snapper CM. 81.  2006. Exosomes from bone marrow dendritic cells pulsed with diphtheria toxoid preferentially induce type 1 antigen-specific IgG responses in naive recipients in the absence of free antigen. J. Immunol. 177:3757–62 [Google Scholar]
  82. Théry C, Boussac M, Veron P, Ricciardi-Castagnoli P, Raposo G. 82.  et al. 2001. Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J. Immunol. 166:7309–18 [Google Scholar]
  83. Näslund TI, Gehrmann U, Qazi KR, Karlsson MCI, Gabrielsson S. 83.  2013. Dendritic cell-derived exosomes need to activate both T and B cells to induce antitumor immunity. J. Immunol. 190:2712–19 [Google Scholar]
  84. Hiltbrunner S, Larssen P, Eldh M, Martinez-Bravo M-J, Wagner AK. 84.  et al. 2016. Exosomal cancer immunotherapy is independent of MHC molecules on exosomes. Oncotarget 7:2538707–17 [Google Scholar]
  85. Del Cacho E, Gallego M, Lee SH, Lillehoj HS, Quilez J. 85.  et al. 2011. Induction of protective immunity against Eimeria tenella infection using antigen-loaded dendritic cells (DC) and DC-derived exosomes. Vaccine 29:213818–25 [Google Scholar]
  86. Aline F, Bout D, Amigorena S, Dimier-Poisson I, Roingeard P. 86.  2004. Toxoplasma gondii antigen-pulsed-dendritic cell-derived exosomes induce a protective immune response against T. gondii infection. Infect. Immun. 72:74127–37 [Google Scholar]
  87. Beauvillain C, Ruiz S, Guiton R, Bout D, Dimier-Poisson I. 87.  2007. A vaccine based on exosomes secreted by a dendritic cell line confers protection against T. gondii infection in syngeneic and allogeneic mice. Microbes Infect 9:1614–22 [Google Scholar]
  88. Smith VL, Cheng Y, Bryant BR, Schorey JS. 88.  2017. Exosomes function in antigen presentation during an in vivo Mycobacterium tuberculosis infection. Sci. Rep. 7:43578 [Google Scholar]
  89. Montecalvo A, Larregina AT, Shufesky WJ, Stolz DB, Sullivan MLG. 89.  et al. 2012. Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 119:3756–66 [Google Scholar]
  90. Alexander M, Hu R, Runtsch MC, Kagele DA, Mosbruger TL. 90.  et al. 2015. Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nat. Commun. 6:7321 [Google Scholar]
  91. Edgar JR, Manna PT, Nishimura S, Banting G, Robinson MS. 91.  2016. Tetherin is an exosomal tether. eLife 5:1–19 [Google Scholar]
  92. Neil SJD. 92.  2013. Intrinsic immunity: the antiviral activities of tetherin. Intrinsic Immunity B Cullen 67–104 Curr. Top. Microbiol. Immunol 371 Berlin: Springer [Google Scholar]
  93. Li SX, Barrett BS, Guo K, Kassiotis G, Hasenkrug KJ. 93.  et al. 2016. Tetherin/BST-2 promotes dendritic cell activation and function during acute retrovirus infection. Sci. Rep. 6:20425 [Google Scholar]
  94. Li SX, Barrett BS, Heilman KJ, Messer RJ, Liberatore RA. 94.  et al. 2014. Tetherin promotes the innate and adaptive cell-mediated immune response against retrovirus infection in vivo. J. Immunol. 193:306–16 [Google Scholar]
  95. Blasius AL, Giurisato E, Cella M, Schreiber RD, Shaw AS, Colonna M. 95.  2006. Bone marrow stromal cell antigen 2 is a specific marker of type I IFN-producing cells in the naive mouse, but a promiscuous cell surface antigen following IFN stimulation. J. Immunol. 177:3260–65 [Google Scholar]
  96. Kim SH, Bianco NR, Shufesky WJ, Morelli AE, Robbins PD. 96.  2007. MHC class II+ exosomes in plasma suppress inflammation in an antigen-specific and Fas ligand/Fas-dependent manner. J. Immunol. 179:2235–41 [Google Scholar]
  97. Ruffner MA, Seon HK, Bianco NR, Francisco LM, Sharpe AH, Robbins PD. 97.  2009. B7–1/2, but not PD-L1/2 molecules, are required on IL-10-treated tolerogenic DC and DC-derived exosomes for in vivo function. Eur. J. Immunol. 39:3084–90 [Google Scholar]
  98. Yang X, Meng S, Jiang H, Chen T, Wu W. 98.  2010. Exosomes derived from interleukin-10-treated dendritic cells can inhibit trinitrobenzene sulfonic acid-induced rat colitis. Scand. J. Gastroenterol. 45:51168–77 [Google Scholar]
  99. Kim SH, Lechman ER, Bianco N, Menon R, Keravala A. 99.  et al. 2005. Exosomes derived from IL-10-treated dendritic cells can suppress inflammation and collagen-induced arthritis. J. Immunol. 174:6440–48 [Google Scholar]
  100. Song J, Chen X, Wang M, Xing Y, Zheng Z, Hu S. 100.  2014. Cardiac endothelial cell-derived exosomes induce specific regulatory B cells. Sci. Rep. 4:7583 [Google Scholar]
  101. Song J, Huang J, Chen X, Teng X, Song Z. 101.  et al. 2016. Donor-derived exosomes induce specific regulatory T cells to suppress immune inflammation in the allograft heart. Sci. Rep. 7:1–11 [Google Scholar]
  102. Buzas EI, György B, Nagy G, Falus A, Gay S. 102.  2014. Emerging role of extracellular vesicles in inflammatory diseases. Nat. Rev. Rheumatol. 10:6356–64 [Google Scholar]
  103. Ullal AJ, Reich CF, Clowse M, Criscione-Schreiber LG, Tochacek M. 103.  et al. 2011. Microparticles as antigenic targets of antibodies to DNA and nucleosomes in systemic lupus erythematosus. J. Autoimmun. 36:3–4173–80 [Google Scholar]
  104. Morelli AE, Larregina AT, Shufesky WJ, Sullivan MLG, Stolz DB. 104.  et al. 2004. Endocytosis, intracellular sorting and processing of exosomes by dendritic cells. Hematology 55027:101–29 [Google Scholar]
  105. Zhou J, Tagaya Y, Tolouei-Semnani R, Schlom J, Sabzevari H. 105.  2005. Physiological relevance of antigen presentasome (APS), an acquired MHC/costimulatory complex, in the sustained activation of CD4+ T cells in the absence of APCs. Blood 105:83238–46 [Google Scholar]
  106. Xia D, Hao S, Xiang J. 106.  2006. CD8+ cytotoxic T-APC stimulate central memory CD8+ T cell responses via acquired peptide-MHC class I complexes and CD80 costimulation, and IL-2 secretion. J. Immunol. 177:2976–84 [Google Scholar]
  107. Umeshappa CS, Huang H, Xie Y, Wei Y, Mulligan SJ. 107.  et al. 2009. CD4+ Th-APC with acquired peptide/MHC class I and II complexes stimulate type 1 helper CD4+ and central memory CD8+ T cell responses. J. Immunol. 182:193–206 [Google Scholar]
  108. Gérard A, Khan O, Beemiller P, Oswald E, Hu J. 108.  et al. 2013. Secondary T cell-T cell synaptic interactions drive the differentiation of protective CD8+ T cells. Nat. Immunol. 14:4356–63 [Google Scholar]
  109. Helft J, Jacquet A, Joncker NT, Grandjean I, Dorothée G. 109.  et al. 2008. Antigen-specific T-T interactions regulate CD4 T-cell expansion. Blood 112:41249–58 [Google Scholar]
  110. Tsang JYS, Chai JG, Lechler R. 110.  2003. Antigen presentation by mouse CD4+ T cells involving acquired MHC class II:peptide complexes: another mechanism to limit clonal expansion?. Blood 101:72704–10 [Google Scholar]
  111. Costantino CM, Spooner E, Ploegh HL, Hafler DA. 111.  2012. Class II MHC self-antigen presentation in human B and T lymphocytes. PLOS ONE 7:11–9 [Google Scholar]
  112. Lasalle JM, Tolentino PJ, Freeman GJ, Nadler LM, Hafler DA. 112.  1992. Early signaling defect in human T cells anergized by T cell presentation of autoantigen. J. Exp. Med. 176:177–86 [Google Scholar]
  113. Patel DM, Arnold PY, White GA, Nardella JP, Mannie MD. 113.  1999. Class II MHC/peptide complexes are released from APC and are acquired by T cell responders during specific antigen recognition. J Immunol 163:5201–10 [Google Scholar]
  114. Fletcher AL, Malhotra D, Turley SJ. 114.  2011. Lymph node stroma broaden the peripheral tolerance paradigm. Trends Immunol 32:112–18 [Google Scholar]
  115. Dubrot J, Duraes FV, Potin L, Capotosti F, Brighouse D. 115.  et al. 2014. Lymph node stromal cells acquire peptide-MHCII complexes from dendritic cells and induce antigen-specific CD4+ T cell tolerance. J. Exp. Med. 211:61153–66 [Google Scholar]
  116. Kambayashi T, Laufer TM. 116.  2014. Atypical MHC class II-expressing antigen-presenting cells: Can anything replace a dendritic cell?. Nat. Rev. Immunol. 14:719–30 [Google Scholar]
  117. Buschow SI, van Balkom BWM, Aalberts M, Heck AJR, Wauben M, Stoorvogel W. 117.  2010. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunol. Cell Biol. 88:8851–56 [Google Scholar]
  118. Wubbolts R, Leckie RS, Veenhuizen PTM, Schwarzmann G, Möbius W. 118.  et al. 2003. Proteomic and biochemical analyses of human B cell-derived exosomes: potential implications for their function and multivesicular body formation. J. Biol. Chem. 278:1310963–72 [Google Scholar]
  119. Escola JM, Kleijmeer MJ, Stoorvogel W, Griffith JM, Yoshie O, Geuze HJ. 119.  1998. Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J. Biol. Chem. 273:3220121–27 [Google Scholar]
  120. Latysheva N, Muratov G, Rajesh S, Padgett M, Hotchin NA. 120.  et al. 2006. Syntenin-1 is a new component of tetraspanin-enriched microdomains: mechanisms and consequences of the interaction of syntenin-1 with CD63. Mol. Cell. Biol. 26:207707–18 [Google Scholar]
  121. Pols MS, Klumperman J. 121.  2008. Trafficking and function of the tetraspanin CD63. Exp. Cell Res. 315:91584–92 [Google Scholar]
  122. Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G. 122.  et al. 2012. Syndecan-syntenin-alix regulates the biogenesis of exosomes. Nat. Cell Biol. 14:7677–85 [Google Scholar]
  123. Nutt SL, Hodgkin PD, Tarlinton DM, Corcoran LM. 123.  2015. The generation of antibody-secreting plasma cells. Nat. Rev. Immunol. 15:3160–71 [Google Scholar]
  124. Vinuesa CG, Linterman MA, Goodnow CC, Randall KL. 124.  2010. T cells and follicular dendritic cells in germinal center B-cell formation and selection. Immunol. Rev. 237:72–89 [Google Scholar]
  125. Yuseff MI, Lennon-Duménil AM. 125.  2015. B cells use conserved polarity cues to regulate their antigen processing and presentation functions. Front. Immunol. 6:1–7 [Google Scholar]
  126. Mitchison NA. 126.  2004. T-cell-B-cell cooperation. Nat. Rev. Immunol. 4:308–12 [Google Scholar]
  127. Arita S, Baba E, Shibata Y, Niiro H, Shimoda S. 127.  et al. 2008. B cell activation regulates exosomal HLA production. Eur. J. Immunol. 38:1423–34 [Google Scholar]
  128. Saunderson SC, Schuberth PC, Dunn AC, Miller L, Hock BD. 128.  et al. 2008. Induction of exosome release in primary B cells stimulated via CD40 and the IL-4 receptor. J. Immunol. 180:8146–52 [Google Scholar]
  129. Momen-Heravi F, Bala S, Bukong T, Szabo G. 129.  2014. Exosome-mediated delivery of functionally active miRNA-155 inhibitor to macrophages. Nanomed. Nanotechnol. Biol. Med. 10:71517–27 [Google Scholar]
  130. Rialland P, Lankar D, Raposo G, Bonnerot C, Hubert P. 130.  2006. BCR-bound antigen is targeted to exosomes in human follicular lymphoma B-cells. Biol. Cell. 98:491–501 [Google Scholar]
  131. Verweij FJ, van Eijndhoven MAJ, Hopmans ES, Vendrig T, Wurdinger T. 131.  et al. 2011. LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-κB activation. EMBO J 30:112115–29 [Google Scholar]
  132. Gutzeit C, Nagy N, Gentile M, Lyberg K, Gumz J. 132.  et al. 2014. Exosomes derived from Burkitt's lymphoma cell lines induce proliferation, differentiation, and class-switch recombination in B cells. J. Immunol. 192:5852–62 [Google Scholar]
  133. Pegtel DM, Cosmopoulos K, Thorley-Lawson DA, van Eijndhoven MAJ, Hopmans ES. 133.  et al. 2010. Functional delivery of viral miRNAs via exosomes. PNAS 107:6328–33 [Google Scholar]
  134. Emerson SG, Cone RE. 134.  1981. I-Kk and H-2Kk antigens are shed as supramolecular particles in association with membrane lipids. J. Immunol. 127:2482–86 [Google Scholar]
  135. Denzer K, van Eijk M, Kleijmeer MJ, Jakobson E, de Groot C, Geuze HJ. 135.  2000. Follicular dendritic cells carry MHC class II-expressing microvesicles at their surface. J. Immunol. 165:1259–65 [Google Scholar]
  136. Papp K, Végh P, Prechl J, Kerekes K, Kovács J. 136.  et al. 2008. B lymphocytes and macrophages release cell membrane deposited C3-fragments on exosomes with T cell response-enhancing capacity. Mol. Immunol. 45:2343–51 [Google Scholar]
  137. Clayton A, Turkes A, Dewitt S, Steadman R, Mason MD, Hallett MB. 137.  2004. Adhesion and signaling by B cell-derived exosomes: the role of integrins. FASEB J 18:2977–79 [Google Scholar]
  138. Wang X, Rodda LB, Bannard O, Cyster JG. 138.  2014. Integrin-mediated interactions between B cells and follicular dendritic cells influence germinal center B cell fitness. J. Immunol. 192:4601–9 [Google Scholar]
  139. Clayton A, Harris CL, Court J, Mason MD, Morgan BP. 139.  2003. Antigen-presenting cell exosomes are protected from complement-mediated lysis by expression of CD55 and CD59. Eur. J. Immunol. 33:522–31 [Google Scholar]
  140. Crotty S. 140.  2014. T follicular helper cell differentiation, function, and roles in disease. Immunity 41:4529–42 [Google Scholar]
  141. Admyre C, Bohle B, Johansson SM, Focke-Tejkl M, Valenta R. 141.  et al. 2007. B cell-derived exosomes can present allergen peptides and activate allergen-specific T cells to proliferate and produce Th2-like cytokines. J. Allergy Clin. Immunol. 120:1418–24 [Google Scholar]
  142. Lundy SK, Klinker MW. 142.  2014. Characterization and activity of Fas ligand producing CD5+ B cells. Methods Mol. Biol. 1190:81–102 [Google Scholar]
  143. Klinker MW, Lizzio V, Reed TJ, Fox DA, Lundy SK. 143.  2014. Human B cell-derived lymphoblastoid cell lines constitutively produce Fas ligand and secrete MHCII+FasL+ killer exosomes. Front. Immunol. 5:1–10 [Google Scholar]
  144. Asano K, Nabeyama A, Miyake Y, Qiu CH, Kurita A. 144.  et al. 2011. CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens. Immunity 34:185–95 [Google Scholar]
  145. Backer R, Schwandt T, Greuter M, Oosting M, Jungerkes F. 145.  et al. 2010. Effective collaboration between marginal metallophilic macrophages and CD8+ dendritic cells in the generation of cytotoxic T cells. PNAS 107:216–21 [Google Scholar]
  146. Schorey JS, Harding CV. 146.  2016. Extracellular vesicles and infectious diseases: new complexity to an old story. J. Clin. Investig. 126:41181–89 [Google Scholar]
  147. Ramachandra L, Qu Y, Wang Y, Lewis CJ, Cobb BA. 147.  et al. 2010. Mycobacterium tuberculosis synergizes with ATP to induce release of microvesicles and exosomes containing major histocompatibility complex class II molecules capable of antigen presentation. Infect. Immun. 78:125116–25 [Google Scholar]
  148. Giri PK, Schorey JS. 148.  2008. Exosomes derived from M. bovis BCG infected macrophages activate antigen-specific CD4+ and CD8+ T cells in vitro and in vivo. PLOS ONE 3:6e2461 [Google Scholar]
  149. Cheng Y, Schorey JS. 149.  2013. Exosomes carrying mycobacterial antigens can protect mice against Mycobacterium tuberculosis infection. Eur. J. Immunol. 43:3279–90 [Google Scholar]
  150. Van Niel G, Mallegol J, Bevilacqua C, Candalh C, Brugière S. 150.  et al. 2003. Intestinal epithelial exosomes carry MHC class II/peptides able to inform the immune system in mice. Gut 52:1690–97 [Google Scholar]
  151. Mallegol J, Van Niel G, Lebreton C, Lepelletier Y, Candalh C. 151.  et al. 2007. T84-intestinal epithelial exosomes bear MHC class II/peptide complexes potentiating antigen presentation by dendritic cells. Gastroenterology 132:1866–76 [Google Scholar]
  152. Büning J, Von Smolinski D, Tafazzoli K, Zimmer KP, Strobel S. 152.  et al. 2008. Multivesicular bodies in intestinal epithelial cells: responsible for MHC class II-restricted antigen processing and origin of exosomes. Immunology 125:510–21 [Google Scholar]
  153. Östman S, Taube M, Telemo E. 153.  2005. Tolerosome-induced oral tolerance is MHC dependent. Immunology 116:464–76 [Google Scholar]
  154. Prado N, Marazuela EG, Segura E, Fernandez-Garcia H, Villalba M. 154.  et al. 2008. Exosomes from bronchoalveolar fluid of tolerized mice prevent allergic reaction. J. Immunol. 181:1519–25 [Google Scholar]
  155. Blanchard N, Lankar D, Faure F, Regnault A, Dumont C. 155.  et al. 2002. TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/ζ complex. J. Immunol. 168:3235–41 [Google Scholar]
  156. Wahlgren J, Karlson TDL, Glader P, Telemo E, Valadi H. 156.  2012. Activated human T cells secrete exosomes that participate in IL-2 mediated immune response signaling. PLOS ONE 7:111–10 [Google Scholar]
  157. Monleon I, Martinez-Lorenzo MJ, Monteagudo L, Lasierra P, Taules M. 157.  et al. 2001. 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. 167:6736–44 [Google Scholar]
  158. Alonso R, Rodríguez MC, Pindado J, Merino E, Mérida I, Izquierdo M. 158.  2005. Diacylglycerol kinase α regulates the secretion of lethal exosomes bearing Fas ligand during activation-induced cell death of T lymphocytes. J. Biol. Chem. 280:3128439–50 [Google Scholar]
  159. Busch A, Quast T, Keller S, Kolanus W, Knolle P. 159.  et al. 2008. Transfer of T cell surface molecules to dendritic cells upon CD4+ T cell priming involves two distinct mechanisms. J Immunol 181:3965–73 [Google Scholar]
  160. Zhang H, Liu L, Wen K, Huang J, Geng S. 160.  et al. 2011. Chimeric flagellin expressed by Salmonella typhimurium induces an ESAT-6-specific Th1-type immune response and CTL effects following intranasal immunization. Cell. Mol. Immunol. 8:6496–501 [Google Scholar]
  161. Gardell JL, Parker DC. 161.  2017. CD40L is transferred to antigen-presenting B cells during delivery of T-cell help. Eur. J. Immunol. 47:41–50 [Google Scholar]
  162. Palucka K, Banchereau J. 162.  2013. Dendritic-cell-based therapeutic cancer vaccines. Immunity 39:138–48 [Google Scholar]
  163. Anguille S, Smits EL, Lion E, Van Tendeloo VF, Berneman ZN. 163.  2014. Clinical use of dendritic cells for cancer therapy. Lancet Oncol 15:257–67 [Google Scholar]
  164. Escudier B, Dorval T, Chaput N, André F, Caby M-P. 164.  et al. 2005. Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase I clinical trial. J. Transl. Med. 3:10 [Google Scholar]
  165. Morse MA, Garst J, Osada T, Khan S, Hobeika A. 165.  et al. 2005. A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J. Transl. Med. 3:9 [Google Scholar]
  166. Besse B, Charrier M, Lapierre V, Dansin E, Lantz O. 166.  et al. 2016. Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology 5:4e1071008 [Google Scholar]
  167. Damo M, Wilson DS, Simeoni E, Hubbell JA. 167.  2015. TLR-3 stimulation improves anti-tumor immunity elicited by dendritic cell exosome-based vaccines in a murine model of melanoma. Sci. Rep. 5:17622 [Google Scholar]
  168. De La Peña H, Madrigal JA, Rusakiewicz S, Bencsik M, Cave GWV. 168.  et al. 2009. Artificial exosomes as tools for basic and clinical immunology. J. Immunol. Methods. 344:2121–32 [Google Scholar]
  169. Srinivasan S, Vannberg FO, Dixon JB. 169.  2016. Lymphatic transport of exosomes as a rapid route of information dissemination to the lymph node. Sci. Rep. 6:24436 [Google Scholar]
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