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Blood, 1 March 2006, Vol. 107, No. 5, pp. 2022-2029.
Prepublished online as a Blood First Edition Paper on November 3, 2005; DOI 10.1182/blood-2005-05-2016.
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Submitted May 19, 2005
Accepted October 18, 2005
CD11c+ dendritic cells (DCs) and plasmacytoid DCs are activated by human cytomegalovirus and retain efficient T cell-stimulatory capability upon infection
Espen O Kvale*, Jakob Dalgaard, Fridtjof Lund-Johansen, Halvor Rollag, Lorant Farkas, Karsten Midtvedt, Frode L Jahnsen, Jan E Brinchmann, and Johanna Olweus
Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, Rikshospitalet University Hospital, Oslo, Norway; Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway
Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway
Institute of Immunology, Rikshospitalet University Hospital, Oslo, Norway; Department of Medicine, Section of Hematology, University of Oslo, Rikshospitalet University Hospital, Oslo, Norway
Institute of Medical Microbiology, Rikshospitalet University Hospital, Oslo, Norway
Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, Rikshospitalet University Hospital, Oslo, Norway
Department of Medicine, Section of Nephrology, University of Oslo, Rikshospitalet University Hospital, Oslo, Norway
* Corresponding author; email: e.o.kvale{at}medisin.uio.no.
Human cytomegalovirus (HCMV) has been suggested to evade the immune system by infecting and paralyzing antigen-presenting cells. This view is mainly based on studies of dendritic cells (DCs) obtained after culture of monocytes (moDCs). It is contradicted by the asymptomatic course of HCMV infection in healthy individuals, indicating that other key antigen-presenting cells induce an efficient immune response. Here, we show that HCMV activates CD11c+ DCs and plasmacytoid dendritic cells (PDCs). In contrast to moDCs, CD11c+ DCs and PDCs produced type I interferon (IFN) when exposed to HCMV. Autocrine type I IFN partially protected CD11c+ DCs against infection, whereas PDCs were resistant to HCMV even when type I IFN activity was inhibited. HCMV exposure induced maturation of CD11c+ DCs by type I IFN-dependent and -independent mechanisms. Importantly, CD11c+ DCs infected by inhibiting type I IFN activity retained full capacity to stimulate T cells. Kidney transplant recipients on immunosuppressive treatment had lower frequencies of CD11c+ DCs and PDCs in blood than healthy individuals. The results show that HCMV activates the immune system by interacting with CD11c+ DCs and PDCs, and that transplant recipients have low frequencies of these cell types in blood.

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