Abbreviations APC antigen-presenting cell CNS central nervous system EAE experimental autoimmune encephalomyelitis IFN-γ γ interferon γ mAb monoclonal antibody MBP myelin basic protein MOG myelin oligodendrocyte glycoprotein MS multiple sclerosis PBMC peripheral-blood mononuclear cell PLP proteolipid protein TNF-α α tumor necrosis factor α
A considerable amount of evidence in EAE models suggests that the B7-CD28/CTLA-4 costimulatory pathways probably play a role in the pathogenesis and/or regulation of MS [4]. Immunohistochemical and flow-cytometric analyses of the in vivo expression of the B7 costimulatory molecules and their receptors during the course of acute disease, remission and relapse have demonstrated that the receptors and ligands in the B7-CD28/CTLA-4 costimulatory pathways are differentially regulated at different times during the course of EAE [5 • ,6 • ]. In the model of EAE induced by proteolipid protein (PLP; this is a component of myelin) 139-151 peptide in SJL mice, B7-1 became the predominant costimulatory ligand expressed following the initial acute clinical episode. In the myelin basic protein (MBP)-induced EAE model in (PLJ x SJL)F1 mice, B7-2 expression was seen during acute disease and during relapse and B7-1 expression was seen only during remission. CD28 was expressed on a large number of cells during acute disease and during relapses, and surface levels of its expression were reduced during disease remission. In contrast, few cells were positive for CTLA-4 expression but