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The Journal of Immunology, 2007, 179: 5024-5032.
Copyright © 2007 by The American Association of Immunologists, Inc.

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Antigen Presentation by Exosomes Released from Peptide-Pulsed Dendritic Cells Is not Suppressed by the Presence of Active CTL1

Lea Luketic*, Jordan Delanghe*, Paul T. Sobol{dagger}, Pingchang Yang*, Erin Frotten*, Karen L. Mossman*, Jack Gauldie*, Jonathan Bramson* and Yonghong Wan2,*

* Department of Pathology and Molecular Medicine and {dagger} Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada

Despite the potency of dendritic cells (DCs) as a vaccine carrier, they are short-lived and sensitive to CTL-mediated elimination. Thus, it is believed that the longevity of Ag presentation by peptide-pulsed DC is limited in vivo. Surprisingly, however, we found that although the majority of injected DCs disappeared from the draining lymph nodes within 7 days, Ag presentation persisted for at least 14 days following DC immunization. This prolonged Ag presentation was not mediated by the remaining injected DCs or through Ag transfer to endogenous APCs. We provide evidence that exosomes released by DCs might be responsible for the persistence of Ag presentation. Functional exosomes could be recovered from the draining lymph nodes of C57BL/6 mice following DC vaccination and, in contrast to DCs, T cell stimulation by exosomes in vivo was not affected by the presence of CTL. Our findings demonstrate that Ag presentation following delivery of DC vaccines persists for longer than expected and indicate that the exosome may play a previously unrecognized role in Ag presentation following DC vaccination. Furthermore, our study reinforces the application of exosomes as a vaccination platform and suggests that exosome-based vaccines may be advantageous for booster immunizations due to their resistance to CTL.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by grants from the Canadian Institutes of Health Research and the Ontario Cancer Research Network. Y.W. is a recipient of a Canadian Institutes of Health Research Scholarship. J.L.B. is supported by an Rx&D Health Research Foundation/Canadian Institutes of Health Research Career Award in Health Research. L.L. was supported by a Canada Institutes of Health Research Master’s Award.

2 Address correspondence and reprint requests to Dr. Yonghong Wan, Department of Pathology and Molecular Medicine, 5024 Michael DeGroote Centre for Learning & Discovery, McMaster University, 1200 Main Street West, Hamilton, Ontario L8N 3Z5, Canada

3 Abbreviations used in this paper: DC, dendritic cell; DCex, DC-derived exosome; LN, lymph node; LCMV, lymphocytic choriomeningitis virus.




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Sci SignalHome page
H. C. O'Neill and B. J. C. Quah
Exosomes Secreted by Bacterially Infected Macrophages Are Proinflammatory
Sci. Signal., February 12, 2008; 1(6): pe8 - pe8.
[Abstract] [Full Text] [PDF]




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