Induction of persistently demyelinated lesions in the rat following the repeated adoptive transfer of encephalitogenic T cells and demyelinating antibody.
A chronic relapsing model of demyelinating experimental allergic encephalomyelitis (EAE) was induced in Lewis rats by the repeated co-transfer of encephalitogenic, myelin basic protein (MBP)-specific T cells in combination with a demyelinating monoclonal antibody (mAb) specific for the myelin oligodendrocyte glycoprotein (MOG). In controls, repeated injections of 5 x 10(5) MBP-specific T cells at intervals of 18-21 days resulted in an increasing resistance to the induction of further episodes of EAE. However, intravenous injection of the mAb 4 days after each T cell transfer overcame this 'vaccination' effect and induced severe clinical relapses associated with an increasing and persistent neurological deficit. Histological examination revealed that four cycles of treatment with T cells and mAb were sufficient to result in the formation of large plaques of demyelination in the spinal cord that failed to undergo significant remyelination within 60 days of the final injection of mAb. These lesions consisted of a matrix of astrocytic scar tissue traversed by numerous naked axons. These observations demonstrate that the formation of large, persistently, demyelinated lesions in a T cell-mediated model of EAE in the Lewis rat is dependent on the presence of an appropriate anti-myelin autoantibody response.
Linington
C
C
Department of Neuroimmunology, Max-Planck-Institute for Psychiatry, Planegg-Martinsried, Germany.
Engelhardt
B
B
Kapocs
G
G
Lassman
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002460:Cell Line; D002493:Central Nervous System Diseases / Q000276:immunology / Q000503:physiopathology; D003711:Demyelinating Diseases / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D005260:Female; D008562:Membrane Glycoproteins / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009420:Nervous System / Q000503:physiopathology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*
D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; C571328:Mog protein, rat; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein