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Article
Nature Medicine  11, 328 - 334 (2005)
Published online: 27 February 2005; | doi:10.1038/nm1197

Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis

Melanie Greter1, Frank L Heppner2, Maria P Lemos3, Bernhard M Odermatt4, Norbert Goebels1, Terri Laufer3, Randolph J Noelle5 & Burkhard Becher1

1  Neuroimmunology Unit, Department of Neurology, University Hospital Zurich, Frauenklinkstrasse 10, CH-8091 Switzerland.

2  Institute of Neuropathology, Department of Pathology, University Hospital Zurich, Schmelzbergstrasse 12, CH-8091 Switzerland.

3  Division of Rheumatology, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA.

4  Institute for Clinical Pathology, Department of Pathology, University Hospital Zurich, Haeldeliweg 4, CH-8091 Switzerland.

5  Department of Microbiology and Immunology, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, New Hampshire 03755, USA.

Correspondence should be addressed to Burkhard Becher burkhard.becher@usz.ch
Immunization with myelin antigens leads to the development of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. The disease can also be induced by the transfer of encephalitogenic CD4+ T helper (TH) lymphocytes into naive mice. These T cells need to re-encounter their cognate antigen in the context of major histocompatibility complex (MHC) class II−bearing antigen-presenting cells (APCs) in order to recognize their target. The cell type and location of the APC mediating T-cell entry into the central nervous system (CNS) remain unknown. Here, we show that APCs of the lymphoreticular system and of the CNS parenchyma are dispensable for the immune invasion of the CNS. We also describe that a discrete population of vessel-associated dendritic cells (DCs) is present in human brain tissue. In mice, CD11c+ DCs alone are sufficient to present antigen in vivo to primed myelin-reactive T cells in order to mediate CNS inflammation and clinical disease development.

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Nature Medicine
ISSN: 1078-8956
EISSN: 1546-170X
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