title: Spontaneously relapsing-remitting experimental autoimmune uveitis in rats allows successful therapeutic oral tolerance induction in ongoing disease.
abstract: Antigen-specific tolerance induction is a desired therapy for uveitis patients. Our relapsing-remitting rat model of experimental autoimmune uveitis (EAU) induced with IRBP peptide R14 enables us to test the effect of oral tolerance on the prevention of relapsing uveitis. We investigated several peptides overlapping the sequence of R14 for prevention and different doses of R14 for therapy to determine the tolerogenic epitope and the most effective therapeutic regimen for uveitis. Lewis rats were immunized with R14-CFA to induce EAU. Oral tolerance was induced prior to immunization (prevention) or after onset of EAU to prevent relapses (therapy). Therapeutic feeding was performed with high and/or low doses of oral antigen for clonal deletion of effector and induction of regulatory T cells. Uveitis was determined clinically and histologically; mesenteric lymph node (mLN) cells of tolerized rats were tested for surface markers, cytokines and Foxp3 expression. Preventive feeding of R14 and its major epitope R16, but none of the overlapping peptides significantly suppressed EAU and also prevented relapses, irrespective of their pathogenicity. Therapeutic feeding with R14 dramatically reduced relapses, while only the consecutive feeding of high and low-dose R14 had an ameliorating effect on the first course of disease. IL-10-producing T cells from mLN decreased after oral tolerization, and with R14-stimulation in vitro the TCRαβ+/Foxp3+ population increased in the low-dose fed group. No mLN population could be clearly assigned to successful oral tolerance induction during active autoimmune uveitis.
authors.affiliation: Section of Immunobiology, Department of Ophthalmology, Klinikum der Universität, Mathildenstr. 8, 80336 München, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Huber
authors.affiliation: Section of Immunobiology, Department of Ophthalmology, Klinikum der Universität, Mathildenstr. 8, 80336 München, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Diedrichs-Möhring
authors.affiliation: Section of Immunobiology, Department of Ophthalmology, Klinikum der Universität, Mathildenstr. 8, 80336 München, Germany. Electronic address: Gerhild.Wildner@med.uni-muenchen.de.
authors.forename: Gerhild
authors.initials: G
authors.lastname: Wildner
mesh_terms: D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D004306:Dose-Response Relationship, Immunologic; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007108:Immune Tolerance / Q000276:immunology*; D007114:Immunization; D007167:Immunotherapy; D008198:Lymph Nodes / Q000473:pathology; D008643:Mesentery / Q000473:pathology; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D011917:Rats, Inbred Lew; D012008:Recurrence; D014605:Uveitis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000628:therapy*
chemical_list: D010455:Peptides
keywords: Oral tolerance; Rat; Relapsing–remitting autoimmunity; T cells; Uveitis