2013-05-23T08:00:03Z http://repub.eur.nl/oai

oai:repub.eur.nl/res/pub/10011 2012-11-14T12:24:46Z org:9802 org:9825 org:9755 org:9746 access:open type:article

urn:NBN:nl:ui:15-1765/10011 2012-11-14T12:24:46 mods http://hdl.handle.net/1765/10011 hdl:1765/10011 urn:NBN:nl:ui:15-1765/10011 Transfer of central nervous system autoantigens and presentation in secondary lymphoid organs text article http://hdl.handle.net/1765/10011 http://repub.eur.nl/res/pub/10011/12421916.pdf application/pdf Filesize: 686 KB born digital Dendritic cells are thought to regulate tolerance induction vs immunization by transferring Ags and peripheral signals to draining lymph nodes (LN). However, whether myelin Ag transfer and presentation in LN occurs during demyelinating brain disease is unknown. In this study, we demonstrate redistribution of autoantigens from brain lesions to cervical LN in monkey experimental autoimmune encephalomyelitis (EAE) and in multiple sclerosis (MS). Immunohistochemical analysis revealed significantly more cells containing myelin Ags in cervical LN of monkeys with EAE compared with those of healthy control monkeys. Myelin Ags were observed in cells expressing dendritic cell/macrophage-specific markers, MHC class II, and costimulatory molecules. Moreover, these cells were directly juxtaposed to T cells, suggesting that cognate interactions between myelin-containing APC and T cells are taking place in brain-draining LN. Indeed, myelin Ag-reactive T cells were observed in cervical LN from marmosets and rhesus monkeys. Importantly, these findings were paralleled by our findings in human tissue. We observed significantly more myelin Ag-containing cells in LN of individuals with MS compared with those of control individuals. These cells expressed APC markers, as observed in marmosets and rhesus monkeys. These findings suggest that during MS and EAE, modulation of T cell reactivity against brain-derived Ags also takes place in cervical LN and not necessarily inside the brain. A major implication is that novel therapeutic strategies may be targeted to peripheral events, thereby circumventing the blood-brain barrier. Vos, A.F. de Vos, de Alex aut Laman, J.D. Laman Jon aut Meurs, M. van Meurs, van Marjan aut Brok, H.P.M. Brok Herbert aut Boven, L.A. Boven Leonie aut Hintzen, R.Q. Hintzen Rogier aut Valk, P. van der Valk, van der Paul aut Ravid, R. Ravid Rivka aut Rensing, S. Rensing Susanne aut Boon, L. Boon Louis aut Hart, B.A. 't Hart, 't Bert aut 08959469X 193153483 119459833 298684837 Erasmus MC: University Medical Center Rotterdam Supporting host sht en English Journal of Immunology 0022-1767 2002-01-01 Neck Animals Humans Research Support, Non-U.S. Gov't *Antigen Presentation Antigen-Presenting Cells/immunology/metabolism/pathology Autoantigens/analysis/*metabolism Axilla Biological Markers/analysis Brain/*immunology/*metabolism/pathology Callithrix Cell Aggregation/immunology Encephalomyelitis, Autoimmune, Experimental/immunology/metabolism/pathology Epitopes, T-Lymphocyte/analysis Inguinal Canal Lymph Nodes/chemistry/*immunology/*metabolism/pathology Macaca fascicularis Multiple Sclerosis/immunology/metabolism/pathology Macaca mulatta Myelin Basic Proteins/analysis/immunology/metabolism Protein Transport/immunology Spleen T-Lymphocytes/chemistry/immunology/pathology Erasmus University Rotterdam oai:repub.eur.nl/res/pub/10011 IR OAIPMH feed (http://repub.eur.nl/oai) 2007-05-08T10:49:39Z 2011-11-23T09:59:13Z http://purl.org/eprint/accessRights/OpenAccess