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* Department of Microbiology and Immunology,
Interdepartmental Graduate Program in Neuroscience, and
Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642
CD11c+ dendritic cells (DCs) are a prominent component of CNS infiltrates in mice with experimental autoimmune encephalomyelitis. However, their role in immunopathogenesis is controversial. In this study, we report that they originate from peripheral hemopoietic cells and exhibit diverse functions that change during the course of acute disease. CNS DCs stimulate naive T cells to proliferate and polarize Th17 responses when harvested shortly following disease onset but are relatively inefficient APC by the time of peak disability. Conversely, they can support CD4+CD25+ T cell-mediated immunosuppression early during experimental autoimmune encephalomyelitis. Such paradoxical functions might reflect dual roles of CNS DCs in promoting local inflammation while setting the stage for remission.
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1 This work was supported by National Multiple Sclerosis Society Grant RG 3866-A-3 and National Institutes of Health Grant NS047687-01A1.
2 Address correspondence and reprint requests to Dr. Benjamin M. Segal, Department of Neurology/Neuroimmunology, University of Rochester School of Medicine, 601 Elmwood Avenue, Box 605, Rochester, NY 14642. E-mail address: Benjamin_Segal{at}urmc.rochester.edu
3 Abbreviations used in this paper: EAE, experimental autoimmune encephalomyelitis; DC, dendritic cell; BMDC, bone marrow DC; MS, multiple sclerosis; MNC, mononuclear cell; MOG, myelin oligodendrocyte glycoprotein; ODN, oligodeoxynucleotide; Treg, CD4+CD25+ regulatory T cell.
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