Induction of hyperacute brain inflammation and demyelination by activated encephalitogenic T cells and a monoclonal antibody specific for a myelin/oligodendrocyte glycoprotein.
CNS demyelinating inflammatory disease can be a multifactorial process mediated by cellular and antibody-mediated immune processes. Myelin basic protein (MBP)-specific T cells and pathogenic 8-18C5 antibody, specific for a myelin/oligodendrocyte glycoprotein (MOG), a minor component of CNS white matter, can coexist in rats without triggering disease. However, transfer of activated MBP-specific T-cells followed by the injection of 8-18C5 antibody resulted in hyperacute disease progression and CNS demyelination. Transfer of activated T cells specific for an irrelevant antigen or transfer of activated but irradiated encephalitogenic T cells did not induce disease in the presence of 8-18C5 antibody. When needle lesions were induced in brains of 8-18C5 antibody treated rats, no enhancement of demyelination was seen around the needle track. Thus, accessibility of the brain parenchyma to 8-18C5 antibody was not sufficient to induce local demyelination. Therefore, it appears that activated encephalitogenic T cells are involved in initiating the 8-18C5 antibody-mediated demyelinating process.
Schluesener
H J
HJ
Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Lider
O
O
Sobel
R A
RA
D000818:Animals; D000911:Antibodies, Monoclonal; D003711:Demyelinating Diseases / Q000209:etiology* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000473:pathology; D007116:Immunization, Passive; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000276:immunology*; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D008562:Membrane Glycoproteins; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D009419:Nerve Tissue Proteins