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Transfer of central nervous system autoantigens and... (2002) Open access

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Titel Transfer of central nervous system autoantigens and presentation in secondary lymphoid organs
Gepubliceerd in Journal of Immunology. ISSN 0022-1767.
Auteur Vos, de A.F. (Alex); Laman, J.D. (Jon); Meurs, van M. (Marjan); Brok, H.P.M. (Herbert); Boven, L.A. (Leonie); Hintzen, R.Q. (Rogier); Valk, van der P. (Paul); Ravid, R. (Rivka); Rensing, S. (Susanne); Boon, L. (Louis); Hart, 't B.A. (Bert)
Datum 2002-01-01
Trefwoord(en) 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
Taal Engels
Type artikel
Samenvatting 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.
Publicatie http://hdl.handle.net/1765/10011
Persistent Identifier urn:NBN:nl:ui:15-1765/10011
Metadata XML
Repository Erasmus Universiteit Rotterdam
Erasmus Universiteit Rotterdam

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