title: Treatment of experimental encephalomyelitis with a peptide analogue of myelin basic protein.
abstract: Following induction of experimental encephalomyelitis with a T-cell clone, L10C1, that is specific for the myelin basic protein epitope p87-99, the inflammatory infiltrate in the central nervous system contains a diverse collection of T cells with heterogeneous receptors. We show here that when clone L10C1 is tolerized in vivo with an analogue of p87-99, established paralysis is reversed, inflammatory infiltrates regress, and the heterogeneous T-cell infiltrate disappears from the brain, with only the T-cell clones that incited disease remaining in the original lesions. We found that antibody raised against interleukin-4 reversed the tolerance induced by the altered peptide ligand. Treatment with this altered peptide ligand selectively silences pathogenic T cells and actively signals for the efflux of other T cells recruited to the site of disease as a result of the production of interleukin-4 and the reduction of tumour-necrosis factor-alpha in the lesion.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University Medical Center, California 94305, USA.
authors.forename: S
authors.initials: S
authors.lastname: Brocke
authors.forename: K
authors.initials: K
authors.lastname: Gijbels
authors.forename: M
authors.initials: M
authors.lastname: Allegretta
authors.forename: I
authors.initials: I
authors.lastname: Ferber
authors.forename: C
authors.initials: C
authors.lastname: Piercy
authors.forename: T
authors.initials: T
authors.lastname: Blankenstein
authors.forename: R
authors.initials: R
authors.lastname: Martin
authors.forename: U
authors.initials: U
authors.lastname: Utz
authors.forename: N
authors.initials: N
authors.lastname: Karin
authors.forename: D
authors.initials: D
authors.lastname: Mitchell
authors.forename: T
authors.initials: T
authors.lastname: Veromaa
authors.forename: A
authors.initials: A
authors.lastname: Waisman
authors.forename: A
authors.initials: A
authors.lastname: Gaur
authors.forename: P
authors.initials: P
authors.lastname: Conlon
authors.forename: N
authors.initials: N
authors.lastname: Ling
authors.forename: P J
authors.initials: PJ
authors.lastname: Fairchild
authors.forename: D C
authors.initials: DC
authors.lastname: Wraith
authors.forename: A
authors.initials: A
authors.lastname: O'Garra
authors.forename: C G
authors.initials: CG
authors.lastname: Fathman
authors.forename: L
authors.initials: L
authors.lastname: Steinman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000276:immunology; D004679:Encephalomyelitis / Q000188:drug therapy* / Q000276:immunology; D000939:Epitopes; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology / Q000627:therapeutic use*; D010243:Paralysis / Q000276:immunology; D010446:Peptide Fragments / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000939:Epitopes; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D015847:Interleukin-4