The Janus face of CNS-directed autoimmune response: a therapeutic challenge

During the past two decades, much interest has focused on the pathogenic role of autoreactive T‐cells recognizing myelin in both multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). The vast majority of data support the hypothesis that EAE and, by analogy, multiple sclerosis are diseases mediated by autoreactive Th1 T‐cells, much as rheumatoid arthritis, autoimmune diabetes, psoriasis or inflammatory bowel disease. Thus, much effort has been put into developing multiple sclerosis therapies that eliminate more or less specifically autoimmune T‐cells or shift the balance from the presumed pathogenic Th1 to the presumed beneficial Th2 phenotype of T‐cells (Noseworthy et al ., 2000). The two currently approved disease modifying treatments, IFN‐β and glatiramer acetate (GA), are thought to exert their beneficial effect in multiple sclerosis at least in part by this mechanism of action.But clinical observations mainly related to the ‘clinical–radiological paradoxon’ indicate that suppression of a deviated immune response may be an inappropriately simplistic approach: (i) multiple sclerosis inflammatory lesions, as depicted with high sensitivity by contrast enhanced magnetic resonance …