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Antigen Transmission by Replicating Antigen-Bearing Dendritic Cells¹

Jun Diao^*,, Erin Winter^*,, Wenhao Chen^*, Feng Xu^* and Mark S. Cattral^2,*,

^* Toronto General Hospital Research Institute, University Health Network, and Department of Surgery, University of Toronto, Ontario, Canada

During steady-state conditions, conventional spleen dendritic cells (DC) turn over every 2–3 days. Recent evidence indicates that in situ proliferation of DC arising from immediate conventional DC precursors is an important contributor to their homeostasis. In this study, we report that replication-competent conventional DC precursors and DC can internalize and transfer model particulate and soluble Ags directly to their DC progeny during cell division. Real-time confocal microscopy and flow cytometry indicated that Ag transmission to progeny was symmetrical, and suggested that other mechanisms of inter-DC Ag transfer were not involved. Soluble protein Ags inherited by DC progeny were presented effectively to Ag-specific T lymphocytes. Furthermore, we show that the number of DC, and the proportion that are actively proliferating, expands several-fold during an immune response against a viral infection. Our results point to an unanticipated mechanism in which DC are continuously replaced from Ag-bearing replication-competent precursor cells that pass Ag molecules onto their progeny through successive cell divisions. Our findings help explain how Ag may persist in a population of DC despite the brief lifespan of individual mature DC.

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 the Canadian Institutes for Health Research and Astellas (to M.S.C.). Presented in part at Immunology 2007, 94th Annual Meeting of the American Association of Immunologists, Miami Beach, FL, May 18, 2007.

² Address correspondence and reprint requests to Dr. Mark S. Cattral, Toronto General Hospital, Robert McEwen Building, 11c-1247, 585 University Avenue, Toronto, Ontario, Canada M5G 2N2. E-mail address: mark.cattral{at}uhn.on.ca

³ Abbreviations used in this paper: DC, dendritic cell; Adv-βgal, adenovirus encoding bacterial β-galactosidase; cDCp, conventional DC precursors.

⁴ The online version of this article contains supplemental material.

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