title: Antigen-specific gene therapy after immunisation reduces the severity of collagen-induced arthritis.
abstract: Reestablishment of tolerance induction in rheumatoid arthritis (RA) would be an optimal treatment with few, if any, side effects. However, to develop such a treatment further insights in the immunological mechanisms governing tolerance are needed. We have developed a model of antigen-specific tolerance in collagen type II (CII) induced arthritis (CIA) using lentivirus-based gene therapy. The immunodominant epitope of CII was inserted into a lentivirus vector to achieve expression on the MHC class II molecule and the lentiviral particles were subsequently intravenously injected at different time points during CIA. Injection of lentiviral particles in early phases of CIA, that is, at day 7 or day 26 after CII immunisation, partially prevented development of arthritis, decreased the serum levels of CII-specific IgG antibodies, and enhanced the suppressive function of CII-specific T regulatory cells. When lentiviral particles were injected during manifest arthritis, that is, at day 31 after CII immunisation, the severity of arthritis progression was ameliorated, the levels of CII-specific IgG antibodies decreased and the proportion of T regulatory cells increased. Thus, antigen-specific gene therapy is effective when administered throughout the inflammatory course of arthritis and offers a good model for investigation of the basic mechanisms during tolerance in CIA.
authors.affiliation: Department of Rheumatology and Inflammatory Research, University of Gothenburg, P.O. Box 480, 405 30 Gothenburg, Sweden.
authors.forename: Tove
authors.initials: T
authors.lastname: Eneljung
authors.affiliation: Department of Rheumatology and Inflammatory Research, University of Gothenburg, P.O. Box 480, 405 30 Gothenburg, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Tengvall
authors.affiliation: Department of Rheumatology and Inflammatory Research, University of Gothenburg, P.O. Box 480, 405 30 Gothenburg, Sweden.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Jirholt
authors.affiliation: Department of Rheumatology and Inflammatory Research, University of Gothenburg, P.O. Box 480, 405 30 Gothenburg, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Henningsson
authors.affiliation: Medical Inflammation Research, Karolinska Institute, 171 77 Stockholm, Sweden.
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.affiliation: Molecular Immunology Unit, Institute of Child Health, UCL, 30 Guilford Street, London WC1N 1EH, UK.
authors.forename: Kenth
authors.initials: K
authors.lastname: Gustafsson
authors.affiliation: Department of Rheumatology and Inflammatory Research, University of Gothenburg, P.O. Box 480, 405 30 Gothenburg, Sweden.
authors.forename: Inger
authors.initials: I
authors.lastname: Gjertsson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001169:Arthritis, Experimental / Q000235:genetics* / Q000276:immunology* / Q000628:therapy; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D024043:Collagen Type II / Q000235:genetics* / Q000276:immunology*; D000939:Epitopes / Q000235:genetics*; D023061:Gene Order; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D007108:Immune Tolerance; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016086:Lentivirus / Q000235:genetics; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D024043:Collagen Type II; D000939:Epitopes; D007074:Immunoglobulin G