| 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 |