title: Specific blockade of CTLA-4/B7 interactions results in exacerbated clinical and histologic disease in an actively-induced model of experimental allergic encephalomyelitis.
abstract: In addition to an antigen-specific signal, T cell activation requires an antigen-independent costimulatory signal provided by interaction of CD28 with B7 (CD80 and CD86) on the APC. By blocking B7 interactions, previous studies demonstrated the requirement for costimulation in the induction of experimental allergic encephalomyelitis (EAE). Recent studies suggest that unlike CD28, CTLA-4 (a second B7 ligand) delivers an inhibitory signal. To address the regulatory role of CTLA-4 in EAE, we used an antibody directed against CTLA-4 administered at the time of disease induction. This resulted in a significantly more severe clinical course and more inflammatory and demyelinating lesions in the CNS of anti-CTLA-4-treated mice. These data suggest that CTLA-4-mediated inhibitory signals can regulate the clinical severity and histologic parameters of neuroautoimmune disease.
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Berkeley 94720, USA. hurwitz@violet.berkeley.edu
authors.forename: A A
authors.initials: AA
authors.lastname: Hurwitz
authors.forename: T J
authors.initials: TJ
authors.lastname: Sullivan
authors.forename: M F
authors.initials: MF
authors.lastname: Krummel
authors.forename: R A
authors.initials: RA
authors.lastname: Sobel
authors.forename: J P
authors.initials: JP
authors.lastname: Allison
mesh_terms: D000069594:Abatacept; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D060908:CTLA-4 Antigen; D006224:Cricetinae; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D018796:Immunoconjugates; D007166:Immunosuppressive Agents / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007166:Immunosuppressive Agents; D000069594:Abatacept