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* Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia;
Department of Microbiology and Immunology;
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia; and
Autoimmunity and Transplantation Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Mouse spleens contain three major dendritic cell (DC) populations: plasmacytoid DC, conventional CD8+CD24+ DC (CD8+ DC), and conventional CD8–CD24– DC (CD8– DC). We have previously shown that CD8+ DC are the major cross-presenting subtype in vivo and are the main inducers of antiviral cytotoxic T lymphocyte responses. Here we show that after depletion of CD8+ DC, the only DC capable of viral Ag presentation was a small subset that expresses CD24 but not CD8. This CD8–CD24+ DC population is greatly expanded in mice treated with the DC growth factor FMS-like tyrosine kinase 3 ligand. The CD8–CD24+ DC represent an immediate precursor of CD8+ DC, as demonstrated by their expression pattern of characteristic markers of CD8+ DC, their capacity to cross-present in vitro, and their conversion into CD8+ DC upon adoptive transfer into recipient mice. Accordingly, the lifespan of transferred CD8–CD24+ DC in vivo was greatly enhanced as compared with terminally differentiated CD8+ DC. Moreover, in a vaccination protocol, CD8–CD24+ DC induced stronger T cell responses and accelerated viral clearance of HSV-1 compared with CD8+ DC. Our results demonstrate that the ability to cross-present first appears in an immediate precursor population of CD8+ DC that does not yet express CD8. The enhanced capacity of CD8–CD24+ DC to induce immune responses upon adoptive transfer makes them an attractive novel tool for DC-based immunotherapies.
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1 This work was supported by the Deutsche Forschungsgemeinschaft (to S.B. and T.G.), the National Health and Medical Research Council of Australia (NHMRC) (to A.L., W.R.H., and J.A.V.), the Howard Hughes Medical Institute (to W.R.H.), an NHMRC Independent Research Institute Infrastructure Support Scheme grant (no. 361646), a Victorian State Government Operational Infrastructure Support grant, a Leukemia and Lymphoma Society Scholarship (to J.A.V.), and the Fondation pour la Recherche Médicale (to E.S.).
2 S.B. and S.P. contributed equally to this work.
3 Address correspondence and reprint requests to Dr. José A. Villadangos and Dr. Elodie Segura, Immunology Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia. E-mail addresses: villadangos{at}wehi.edu.au and segura{at}wehi.edu.au
4 Abbreviations used in this paper: DC, dendritic cell; pDC, plasmacytoid DC; cDC, conventional DC; Flt3-L, FMS-like tyrosine kinase 3 ligand; B6, C57BL/6.
This article has been cited by other articles:
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  E. Segura, J. Wong, and J. A. Villadangos Cutting Edge: B220+CCR9- Dendritic Cells Are Not Plasmacytoid Dendritic Cells but Are Precursors of Conventional Dendritic Cells J. Immunol., August 1, 2009; 183(3): 1514 - 1517. [Abstract] [Full Text] [PDF]
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