Brain Advance Access published online on March 2, 2006
Brain, doi:10.1093/brain/awl043
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1 Department of Neurology, Medical University of Lodz, Lodz, Poland
* To whom correspondence should be addressed. Plasmacytoid dendritic cells (pDCs) represent a DC subtype that exerts divergent functions in innate and adoptive immunity including the immediate reaction to microbial factors and the induction of immunoregulatory responses. It is thought that different DC subtypes may be critically involved in the pathogenesis of multiple sclerosis (MS). In our study we assessed the phenotype, maturation and functional properties of peripheral blood pDCs from 35 clinically stable, untreated multiple sclerosis patients, 30 healthy controls and 9 patients with pneumonia, which was used as a non-specific inflammatory condition (NIC). Ex vivo expression of CD86 and 4-1BBL was significantly lower on pDCs from multiple sclerosis patients than from controls and patients with NIC (22 versus 47 versus 41% and 12 versus 35 versus 32%, respectively). When stimulated with IL-3 and CD40L, pDCs of multiple sclerosis patients showed inefficient maturation as demonstrated by significantly lower or delayed upregulation of CD86, 4-1BBL, CD40 and CD83. Additionally, in multiple sclerosis, stimulation of pDCs by unmethylated cytosine-phosphate-guanosine oligodeoxynucleotides (CpG ODN) resulted in a significantly lower interferon (IFN) alpha secretion than in controls. In multiple sclerosis, but not in controls, pDCs failed to upregulate proliferative responses and IFN-gamma secretion of autologous peripheral blood mononuclear cells (PBMC) in a co-culture system. Moreover, depletion of pDCs in multiple sclerosis patients, but not in controls, had no effect on generation of CD4+Foxp3+ regulatory T cells. We also provide data showing that glatiramer acetate (GA) treatment partially restores phenotype and function of pDCs in multiple sclerosis patients. These findings suggest functional abnormalities of pDCs in these patients, which might be of importance in the understanding of the development of immune dysregulation in this disease. *Both authors contributed equally to the work.
Received July 26, 2005
Revised November 22, 2005
Accepted January 25, 2006
Article
Impaired maturation and altered regulatory function of plasmacytoid dendritic cells in multiple sclerosis
Mariusz Stasiolek 1 *,
Antonios Bayas 2 *,
Niels Kruse 3,
Anja Wieczarkowiecz 3,
Klaus V. Toyka 4,
Ralf Gold 5 
,
and
Krzysztof Selmaj 1 *
2 Department of Neurology, University of Würzburg, Würzburg, Germany; Department of Neurology, Klinikum Augsburg, Germany
3 Institute for MS Research, Medical Faculty of the University and Gemeinnuetzige Hertie-Stiftung, Goettingen, Germany
4 Department of Neurology, University of Würzburg, Würzburg, Germany
5 Department of Neurology, University of Würzburg, Würzburg, Germany; Institute for MS Research, Medical Faculty of the University and Gemeinnuetzige Hertie-Stiftung, Goettingen, Germany
Krzysztof Selmaj, E-mail: kselmaj{at}afazja.am.lodz.pl
Abstract Both senior authors contributed equally to the work.
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