Encephalitogenic and neuritogenic T cell responses to the myelin-associated glycoprotein (MAG) in the Lewis rat

Autoimmune responses to the myelin-associated glycoprotein (MAG) are implic ated in the immunopathogenesis of both multiple sclerosis (MS) and certain peripheral neuropathies. in this study we demonstrate that T cell responses to defined epitopes of MAG mediate a pathological inflammatory response in the nervous system of the Lewis rat. Peptide-specific T cells were generat ed against four different MAG epitopes, three of which are common to both L - and S-isoforms of MAG (amino acid (a.a.) sequence: 20-34, 124-137, 354-37 7) whilst the fourth epitope (a.a. sequence: 570-582) is located in the C-t erminal sequence of S-MAG. The adoptive transfer of T cells specific for th ese epitopes initiated a mild but dose-dependent inflammatory response in t he central nervous system (CNS) of naive recipients. Clinical disease was o nly observed in those animals injected with T cells specific for the a.a. s equence 20-34 (MP1.1), which also initiated an inflammatory response in the peripheral nervous system (PNS). Go-transfer of MP1.1 (a.a. sequence 20-34 )-specific T cells with the myelin oligodendrocyte glycoprotein (MOG)-speci fic monoclonal antibody 8-18C5 enhanced disease severity and induced widesp read demyelination in the CNS. In contrast, co-transfer of T cells with the MAG-specific mAb 513 failed to induce demyelination, but had a moderate ef fect on the local inflammatory response. The ability of MAG to initiate an autoaggressive T cell response in the Lewis rat supports the concept that M AG-specific autoimmune responses may play a role in the pathogenesis of imm une mediated diseases of the nervous system in man. (C) 1999 Elsevier Scien ce B.V. All rights reserved.