Antigen-loaded exosomes alone induce Th1-type memory through a B cell–dependent mechanism
| Autor: | Ulf Gehrmann, Susanne Gabrielsson, Mikael C. I. Karlsson, Khaleda Rahman Qazi, Emilie Domange Jordö |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Lipopolysaccharides
Ovalbumin Receptors Antigen T-Cell alpha-beta Immunology Antigen presentation B-Lymphocyte Subsets Mice Transgenic macromolecular substances Biology Exosomes Lymphocyte Activation Biochemistry Exosome Interferon-gamma Mice Immune system Antigen In vivo Agammaglobulinaemia Tyrosine Kinase medicine Animals Antigens B cell Mice Knockout Antigen Presentation Lymphokines Mice Inbred BALB C fungi Dendritic Cells Cell Biology Hematology Protein-Tyrosine Kinases Th1 Cells Adoptive Transfer Peptide Fragments In vitro Microvesicles Cell biology carbohydrates (lipids) medicine.anatomical_structure Immunoglobulin G Female Immunization Immunologic Memory |
| Zdroj: | Blood. 113:2673-2683 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2008-04-153536 |
| Popis: | Exosomes are nanovesicles harboring proteins important for antigen presentation. We compared the potency of differently loaded exosomes, directly loaded with OVA323-339 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-γ 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. |
| Databáze: | OpenAIRE |
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