THE IMMUNOLOGY OF MULTIPLE-SCLEROSIS - NEW INTRICACIES AND NEW INSIGHTS

New epidemiology and genetics data have supported the broad concept that multiple sclerosis represents an acquired autoimmunity, which is determined in part by inheritance. Furthermore, it is now widely believed that the pathogenesis of multiple sclerosis involves autoimmune reactivity that is directed against myelin proteins. Much of our understanding of myelin-directed autoimmunity has come from studies on experimental autoimmune encephalomyelitis, a T-cell-mediated, multiple sclerosis-like disease, which is provoked by immunizing animals with myelin proteins. During the past year, significant progress has been made in delineating immune reactivity to myelin antigens. Models that feature restricted epitope recognition and limited T-cell receptor gene utilization have been challenged (often by their original authors). Unifying new concepts include dynamic temporal diversification of the autoimmune response and clear-cut distinctions between the potential and engaged autoimmune repertoire. An abundance of new information about the biologic determinants of T-cell immunopathogenicity is leading rapidly to innovative therapeutic strategies.