title: Antigen-loaded exosomes alone induce Th1-type memory through a B-cell-dependent mechanism.
abstract: Exosomes are nanovesicles harboring proteins important for antigen presentation. We compared the potency of differently loaded exosomes, directly loaded with OVA(323-339) peptide (Pep-Exo) or exosomes from OVA-pulsed DCs (OVA-Exo), for their ability to induce specific T-cell proliferation in vitro and in vivo. Both Pep-Exo and OVA-Exo elicited specific transgenic T-cell proliferation in vitro, with the Pep-Exo being more efficient. In contrast, only OVA-Exo induced specific T-cell responses in vivo highlighting the importance of indirect loading strategies in clinical applications. Coadministration of whole OVA overcame the unresponsiveness with Pep-Exo but still elicited a lower response compared with OVA-Exo. In parallel, we found that OVA-Exo not only augmented the specific T-cell response but also gave a Th1-type shift and an antibody response even in the absence of whole OVA. We detected IgG2a and interferon-gamma production from splenocytes showing the capability of exosomes to provide antigen for B-cell activation. Furthermore, we found that B cells are needed for exosomal T-cell stimulation because Bruton tyrosine kinase-deficient mice showed abrogated B- and T-cell responses after OVA-Exo immunization. These findings reveal that exosomes are potent immune regulators and are relevant for the design of vaccine adjuvants and therapeutic intervention strategies to modulate immune responses.
authors.affiliation: Department of Medicine, Clinical Allergy Research Unit, Karolinska University Hospital Solna, Stockholm, Sweden. khaleda.qazi@ki.se
authors.forename: Khaleda Rahman
authors.initials: KR
authors.lastname: Qazi
authors.forename: Ulf
authors.initials: U
authors.lastname: Gehrmann
authors.forename: Emilie
authors.initials: E
authors.lastname: Domange Jordö
authors.forename: Mikael C I
authors.initials: MC
authors.lastname: Karlsson
authors.forename: Susanne
authors.initials: S
authors.lastname: Gabrielsson
mesh_terms: D019264:Adoptive Transfer; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000941:Antigens / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D055354:Exosomes / Q000276:immunology*; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D000941:Antigens; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D008222:Lymphokines; C111390:OVA 323-339; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma; D010047:Ovalbumin; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse