Antigen-loaded exosomes alone induce Th1-type memory through a B-cell-dependent mechanism (original) (raw)
dependent mechanism − cell Antigen-loaded exosomes alone induce Th1-type memory through a B http://bloodjournal.hematologylibrary.org/content/113/12/2673.full.html Updated information and services can be found at: (4921 articles) Immunobiology Articles on similar topics can be found in the following Blood collections http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#repub\_requests Information about reproducing this article in parts or in its entirety may be found online at: http://bloodjournal.hematologylibrary.org/site/misc/rights.xhtml#reprints Information about ordering reprints may be found online at: http://bloodjournal.hematologylibrary.org/site/subscriptions/index.xhtml Information about subscriptions and ASH membership may be found online at: 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 Tcell 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-␥ production from splenocytes showing the capability of exosomes to provide antigen for B-cell activa-tion. Furthermore, we found that B cells are needed for exosomal T-cell stimulation because Bruton tyrosine kinasedeficient 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. (Blood. 2009;113:2673-2683) Methods Mice BALB/c and DO11.10 OVA TCR transgenic mice (The Jackson Laboratory, Bar Harbor, ME) 18 were kept and bred at the animal facility at the Department of Microbiology, Tumor and Cell Biology (MTC; Karolinska Institutet, Stockholm, Sweden). Age-and sex-matched mice of 6 to 8 weeks
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