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Multiple sclerosis: reduced proportion of circulating plasmacytoid dendritic cells expressing BDCA-2 and BDCA-4 and reduced production of IL-6 and IL-10 in response to herpes simplex virus type 1Department of Neuroscience, Institute of Clinical Neurology, University of Sassari, Sassari, Italy alexsanna72{at}yahoo.it
Department of Neuroscience, Neurology, Uppsala University Hospital, 751 85 Uppsala, Sweden
Department of Neuroscience, Institute of Clinical Neurology, University of Sassari, Sassari, Italy
Department of Neuroscience, Institute of Clinical Neurology, University of Sassari, Sassari, Italy
Department of Neurology, Karolinska Institute, 141 86 Stockholm, Sweden
Department of Neuroscience, Institute of Clinical Neurology, University of Sassari, Sassari, Italy
Department of Neuroscience, Institute of Clinical Neurology, University of Sassari, Sassari, Italy Objective We hypothesized that autoaggressive immune responses observed in multiple sclerosis (MS) could be associated with an imbalance in proportion of immune cell subsets and in cytokine production in response to infection, including viruses. Methods
We collected blood mononuclear cells (MNC) from 23 patients with MS and 23 sex- and age-matched healthy controls (HC) from the island of Sardinia, Italy, where the prevalence of MS is extraordinarily high. Using flow cytometry, we studied MNC for expression of blood dendritic cell antigens (BDCA)-2 and BDCA-4 surface markers reflecting the proportion of plasmacytoid dendritic cells (pDC) that produce type I interferons (IFNs) after virus challenge and promote Th2/anti-inflammtory cytokine production. In parallel, pro-inflammatory (interleukin [IL]-2, IL-12, IFN- Results
The subset of lineage negative (lin–), BDCA-2+ cells was lower in patients with MS compared with HC (0.08 ± 0.02% vs 0.24 ± 0.02%; P < 0.001). A similar pattern was observed for lin–BDCA-4+ cells (0.08 ± 0.02% vs 0.17% ± 0.03; P < 0.01). Spontaneous productions of IL-6 (45 ± 10 pg/mL vs 140 ± 26 pg/mL; P < 0.01) and IL-10 (17 ± 0.4 pg/mL vs 21 ± 1 pg/mL; P < 0.05) by MNC were lower in patients with MS compared with HC. Spontaneous production of IL-6 (6.5 ± 0.15 pg/mL vs 21 ± 5 pg/mL; P < 0.01 and IL-10 (11 ± 1 pg/mL vs 14 ± 3 pg/mL; P < 0.05) by pDC was also lower in patients with MS compared with HC. Exposure of MNC to HSV-1 showed, in both patients with MS and HC, increased production of IFN- Conclusion The results implicate a new evidence for altered immune cells and reduced immune responses in response to viral challenge in MS.
Key Words: herpes simplex virus • IL-6 • IL-12 • multiple sclerosis • plasmacytoid dendritic cells
This version was published on November
1, 2008 Multiple Sclerosis, Vol. 14, No. 9,
1199-1207 (2008) |
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), anti-inflammatory (IL-4, IL-10), and immuno-regulatory/pleiotropic cytokines (type I IFNs including IFN-
and β, IL-6) were measured before and after an in vitro exposure to herpes simplex virus type 1 (HSV-1).