Conditional DC depletion does not affect priming of encephalitogenic Th cells in EAE.
EAE, an animal model for multiple sclerosis, is a Th17- and Th1-cell-mediated auto-immune disease, but the mechanisms leading to priming of encephalitogenic T cells in autoimmune neuroinflammation are poorly understood. To investigate the role of dendritic cells (DCs) in the initiation of autoimmune Th17- and Th1-cell responses and EAE, we used mice transgenic for a simian diphtheria toxin receptor (DTR) expressed under the control of the murine CD11c promoter (CD11c-DTR mice o nC57BL/6 background).EAE was induced by immunization with myelin oligodendrocyte glycoprotein (MOG) protein in CFA. DCs were depleted on the day before and 8 days after MOG immunization. The mean clinical EAE score was only mildly reduced in DC-depleted mice when DCs were ablated before EAE induction. The frequency of activated Th cells was not altered, and MOG-induced Th17 or Th1-cell responses were not altered, in the spleens of DC-depleted mice. Similar results were obtained if DCs were ablated the first 10 days after MOG immunization with repeated DC depletions. Unexpectedly, transient depletion of DCs did not affect priming or differentiation of MOG-induced Th17 and Th1-cell responses or the incidence of EAE. Thus, the mechanism of priming of Th cells in EAE remains to be elucidated.
Department of Medical Sciences, Uppsala University, University Hospital, Uppsala, Sweden.
Magnus
M
Isaksson
Brita Ardesjö
BA
Lundgren
Kerstin M
KM
Ahlgren
Olle
O
Kämpe
Anna
A
Lobell
D000818:Animals; D039521:CD11c Antigen / Q000235:genetics; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D004167:Diphtheria Toxin / Q000008:administration & dosage; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009103:Multiple Sclerosis / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology; D011401:Promoter Regions, Genetic; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
D039521:CD11c Antigen; D004167:Diphtheria Toxin; C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein