Autoimmune encephalomyelitis and uveitis induced by T cell immunity to self beta-synuclein

Abstract

Beta-synuclein is a neuronal protein that accumulates in the plaques that characterize neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. It has been proposed that immunization to peptides of plaque-forming proteins might be used therapeutically to help dissociate pathogenic plaques in the brain. We now report that immunization of Lewis rats with a peptide from beta-synuclein resulted in acute paralytic encephalomyelitis and uveitis. T cell lines and clones reactive to the peptide adoptively transferred the disease to naive rats. Immunoblotting revealed the presence of beta-synuclein in heavy myelin, indicating that the expression of beta-synuclein is not confined to neurons. These results add beta-synuclein to the roster of encephalitogenic self Ags, point out the potential danger of therapeutic autoimmunization to beta-synuclein, and alert us to the unsuspected possibility that autoimmunity to beta-synuclein might play an inflammatory role in the pathogenesis of neurodegeneration.