title: Selective depletion of myelin-reactive T cells with the anti-OX-40 antibody ameliorates autoimmune encephalomyelitis.
abstract: The OX-40 protein was selectively upregulated on encephalitogenic myelin basic protein (MBP)-specific T cells at the site of inflammation during the onset of experimental autoimmune encephalomyelitis (EAE). An OX-40 immunotoxin was used to target and eliminate MBP-specific T cells within the central nervous system without affecting peripheral T cells. When injected in vivo, the OX-40 immunotoxin bound exclusively to myelin-reactive T cells isolated from the CNS, which resulted in amelioration of EAE. Expression of the human OX-40 antigen was also found in peripheral blood of patients with acute graft-versus-host disease and the synovia of patients with rheumatoid arthritis during active disease. The unique expression of the OX-40 molecule may provide a novel therapeutic strategy for eliminating autoreactive CD4+T cells that does not require prior knowledge of the pathogenic autoantigen.
authors.affiliation: Veterans Affairs Medical Center, Portland, Oregon 97207, USA.
authors.forename: A D
authors.initials: AD
authors.lastname: Weinberg
authors.forename: D N
authors.initials: DN
authors.lastname: Bourdette
authors.forename: T J
authors.initials: TJ
authors.lastname: Sullivan
authors.forename: M
authors.initials: M
authors.lastname: Lemon
authors.forename: J J
authors.initials: JJ
authors.lastname: Wallin
authors.forename: R
authors.initials: R
authors.lastname: Maziarz
authors.forename: M
authors.initials: M
authors.lastname: Davey
authors.forename: F
authors.initials: F
authors.lastname: Palida
authors.forename: W
authors.initials: W
authors.lastname: Godfrey
authors.forename: E
authors.initials: E
authors.lastname: Engleman
authors.forename: R J
authors.initials: RJ
authors.lastname: Fulton
authors.forename: H
authors.initials: H
authors.lastname: Offner
authors.forename: A A
authors.initials: AA
authors.lastname: Vandenbark
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002469:Cell Separation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage*; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D012276:Ricin / Q000008:administration & dosage*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood / Q000276:immunology*
chemical_list: D000922:Immunotoxins; D004676:Myelin Basic Protein; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; C505718:Tnfrsf4 protein, rat; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D012276:Ricin