| First Author | Qazi KR | Year | 2009 |
| Journal | Blood | Volume | 113 |
| Issue | 12 | Pages | 2673-83 |
| PubMed ID | 19176319 | Mgi Jnum | J:146517 |
| Mgi Id | MGI:3837867 | Doi | 10.1182/blood-2008-04-153536 |
| Citation | Qazi KR, et al. (2009) Antigen-loaded exosomes alone induce Th1-type memory through a B cell-dependent mechanism. Blood 113(12):2673-83 |
| abstractText | 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. |
