The Journal of Experimental Medicine
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Published 17 February 2004. doi:10.1084/jem.20031059
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 4, 567-579
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CpG-matured Murine Plasmacytoid Dendritic Cells Are Capable of In Vivo Priming of Functional CD8 T Cell Responses to Endogenous but Not Exogenous Antigens

Mariolina Salio1, Michael J. Palmowski1, Ann Atzberger2, Ian F. Hermans1, and Vincenzo Cerundolo1

1 Cancer Research Tumor Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS Oxford, UK
2 Medical Research Council Hematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, OX3 9DS Oxford, UK

Address correspondence to Mariolina Salio, Cancer Research Tumor Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headley Way, OX3 9DS Oxford, UK. Phone: 44-1865-222413; Fax: 44-1865-222502; email: mariolina.salio{at}imm.ox.ac.uk or Vincenzo Cerundolo. Phone: 44-1865-222412; email: vincenzo.cerundolo{at}imm.ox.ac.uk

Plasmacytoid dendritic cells (PDCs) are a unique leukocyte population capable of secreting high levels of type I interferon (IFN) in response to viruses and bacterial stimuli. In vitro experiments have shown that upon maturation, human and murine PDCs develop into potent immunostimulatory cells; however, their ability to prime an immune response in vivo remains to be addressed. We report that CpG-matured murine PDCs are capable of eliciting in naive mice antigen-specific CTLs against endogenous antigens as well as exogenous peptides, but not against an exogenous antigen. Type I IFN is not required for priming, as injection of CpG-matured PDCs into type I IFN receptor–deficient mice elicits functional CTL responses. Mature PDCs prime CTLs that secrete IFN-{gamma} and protect mice from a tumor challenge. In contrast, immature PDCs are unable to prime antigen-specific CTLs. However, mice injected with immature PDCs are fully responsive to secondary antigenic challenges, suggesting that PDCs have not induced long-lasting tolerance via anergic or regulatory T cells. Our results underline the heterogeneity and plasticity of different antigen-presenting cells, and reveal an important role of mature PDCs in priming CD8 responses to endogenous antigens, in addition to their previously reported ability to modulate antiviral responses via type I IFN.

Key Words: PDC • T cell priming • type I IFN • H-Y • tetramers

Abbreviations used in this paper: CFSE, carboxyfluorescein succinimidyl ester; FLT3-L, FLT3 ligand; MCMV, murine cytomegalovirus; MDC, myeloid DC; PDC, plasmacytoid DC.

The online version of this article includes supplemental material.


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