Antigen-loaded exosomes alone induce Th1-type memory through a B-cell-dependent mechanism.
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.
Qazi
Khaleda Rahman
KR
Department of Medicine, Clinical Allergy Research Unit, Karolinska University Hospital Solna, Stockholm, Sweden. khaleda.qazi@ki.se
Gehrmann
Ulf
U
Domange Jordö
Emilie
E
Karlsson
Mikael C I
MC
Gabrielsson
Susanne
S
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*
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