Submitted April 25, 2008
Accepted January 15, 2009
Antigen loaded exosomes alone induce Th1 type memory through a B-cell dependent mechanism
Khaleda Rahman Qazi*, Ulf Gehrmann, Emilie Domange Jordo, Mikael C.I. Karlsson, and Susanne Gabrielsson
Department of Medicine, Clinical Allergy Research Unit, Karolinska University Hospital Solna, Stockholm, Sweden
* Corresponding author; email: khaleda.qazi{at}ki.se.
Exosomes are nano-vesicles harbouring 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 to OVA-Exo. Parallely 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 IFN-
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 since Btk 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.
