title: Epitope spreading is not required for relapses in experimental autoimmune encephalomyelitis.
abstract: The sequential emergence of specific T lymphocyte-mediated immune reactivity directed against multiple distinct myelin epitopes (epitope spreading) has been associated with clinical relapses in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Based on this association, an appealing and plausible model for immune-mediated progression of the advancing clinical course in MS and EAE has been proposed in which epitope spreading is the cause of clinical relapses in T cell-mediated CNS inflammatory diseases. However, the observed association between epitope spreading and disease progression is not universal, and absolute requirements for epitope spreading in progressive EAE have not been tested in the absence of multiple T cell specificities, because most prior studies have been conducted in immunocompetent mouse strains that possessed broad TCR repertoires. Consequently, the precise nature of a causal relationship between epitope spreading and disease progression remains uncertain. To determine whether relapsing or progressive EAE can occur in the absence of epitope spreading, we evaluated the course of disease in mice which possessed only a single myelin-specific TCR. These mice (transgenic/SCID +/+) exhibited a progressive and sometimes remitting/relapsing disease course in the absence of immune reactivity to multiple, spreading myelin epitopes. The results provide direct experimental evidence relevant to discussions on the mechanisms of disease progression in MS and EAE.
authors.affiliation: Veterans Affairs Medical Center, Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA. jonesric@ohsu.edu
authors.forename: Richard E
authors.initials: RE
authors.lastname: Jones
authors.forename: Dennis
authors.initials: D
authors.lastname: Bourdette
authors.forename: Nicole
authors.initials: N
authors.lastname: Moes
authors.forename: Arthur
authors.initials: A
authors.lastname: Vandenbark
authors.forename: Alex
authors.initials: A
authors.lastname: Zamora
authors.forename: Halina
authors.initials: H
authors.lastname: Offner
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D003289:Convalescence; D003433:Crosses, Genetic; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology*; D006183:H-2 Antigens / Q000096:biosynthesis; D017710:Lymphocyte Transfusion; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D012008:Recurrence; D013154:Spleen / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000637:transplantation
chemical_list: D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C405723:myelin basic protein Ac1-11(4Y)