Autoimmune encephalomyelitis and uveitis induced by T cell immunity to self beta-synuclein.
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.
Mor
Felix
F
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. felix.mor@weizmann.ac.il
Quintana
Francisco
F
Mimran
Avishai
A
Cohen
Irun R
IR
D019264:Adoptive Transfer; D020816:Amino Acid Motifs / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000008:administration & dosage / Q000276:immunology*; D002460:Cell Line / Q000637:transplantation; D002999:Clone Cells / Q000637:transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000008:administration & dosage / Q000276:immunology; D007114:Immunization / Q000379:methods; D007279:Injections, Subcutaneous; D008969:Molecular Sequence Data; D009186:Myelin Sheath / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D051843:Synucleins; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014605:Uveitis / Q000276:immunology* / Q000473:pathology; D051846:beta-Synuclein
D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C497609:Sncb protein, rat; D051843:Synucleins; D051846:beta-Synuclein