The Journal of Experimental Medicine
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Published 7 April 2003. doi:10.1084/jem.20021522
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© Rockefeller University Press, 0022-1007/2003/4/885 $5.00
The Journal of Experimental Medicine, Volume 197, Number 7, 885-898

Dendritic Cell Responses to Early Murine Cytomegalovirus Infection : Subset Functional Specialization and Differential Regulation by Interferon {alpha}



Marc Dalod1, Tanya Hamilton1, Rachelle Salomon1, Thais P. Salazar-Mather1, Stanley C. Henry2, John D. Hamilton2 and Christine A. Biron1

1 Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, Providence, RI 02912
2 Department of Veterans Affairs, Medical Research Service and the Research Center on AIDS and HIV Infection, Durham, NC 27705

Address correspondence to Dr. Christine A. Biron, Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Box G-B629, Brown University, Providence, RI 02912. Phone: 401-863-2921; Fax: 401-863-9045; E-mail: Christine_Biron{at}Brown.edu

Differentiation of dendritic cells (DCs) into particular subsets may act to shape innate and adaptive immune responses, but little is known about how this occurs during infections. Plasmacytoid dendritic cells (PDCs) are major producers of interferon (IFN)-{alpha} in response to many viruses. Here, the functions of these and other splenic DC subsets are further analyzed after in vivo infection with murine cytomegalovirus (MCMV). Viral challenge induced PDC maturation, their production of high levels of innate cytokines, and their ability to activate natural killer (NK) cells. The conditions also licensed PDCs to efficiently activate CD8 T cells in vitro. Non-plasmacytoid DCs induced T lymphocyte activation in vitro. As MCMV preferentially infected CD8{alpha}+ DCs, however, restricted access to antigens may limit plasmacytoid and CD11b+ DC contribution to CD8 T cell activation. IFN-{alpha} regulated multiple DC responses, limiting viral replication in all DC and IL-12 production especially in the CD11b+ subset but promoting PDC accumulation and CD8{alpha}+ DC maturation. Thus, during defense against a viral infection, PDCs appear specialized for initiation of innate, and as a result of their production of IFN-{alpha}/ß, regulate other DCs for induction of adaptive immunity. Therefore, they may orchestrate the DC subsets to shape endogenous immune responses to viruses.

Key Words: plasmacytoid dendritic cell • interferon {alpha}/ß • murine cytomegalovirus • antigen presentation • CD8 T lymphocyte


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