title: Gene Therapy Induces Antigen-Specific Tolerance in Experimental Collagen-Induced Arthritis.
abstract: Here, we investigate induction of immunological tolerance by lentiviral based gene therapy in a mouse model of rheumatoid arthritis, collagen II-induced arthritis (CIA). Targeting the expression of the collagen type II (CII) to antigen presenting cells (APCs) induced antigen-specific tolerance, where only 5% of the mice developed arthritis as compared with 95% of the control mice. In the CII-tolerized mice, the proportion of Tregs as well as mRNA expression of SOCS1 (suppressors of cytokine signaling 1) increased at day 3 after CII immunization. Transfer of B cells or non-B cell APC, as well as T cells, from tolerized to naïve mice all mediated a certain degree of tolerance. Thus, sustainable tolerance is established very early during the course of arthritis and is mediated by both B and non-B cells as APCs. This novel approach for inducing tolerance to disease specific antigens can be used for studying tolerance mechanisms, not only in CIA but also in other autoimmune diseases.
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Tengvall
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.|Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Tove
authors.initials: T
authors.lastname: Eneljung
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Pernilla
authors.initials: P
authors.lastname: Jirholt
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Olof
authors.initials: O
authors.lastname: Turesson
authors.affiliation: Medical Inflammation Research, Dept of medical Biochemistry and biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kajsa
authors.initials: K
authors.lastname: Wing
authors.affiliation: Medical Inflammation Research, Dept of medical Biochemistry and biophysics, Karolinska Institutet, Stockholm, Sweden.|Southern Medical University, Guangzhou, PR China.
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.affiliation: Department of Chemistry, BMC, Uppsala University, Uppsala, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Kihlberg
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Stern
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Inga-Lill
authors.initials: IL
authors.lastname: Mårtensson
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Henningsson
authors.affiliation: Molecular and Cellular Immunology Section, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Kenth
authors.initials: K
authors.lastname: Gustafsson
authors.affiliation: Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.|Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Inger
authors.initials: I
authors.lastname: Gjertsson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000941:Antigens / Q000276:immunology*; D001169:Arthritis, Experimental / Q000097:blood / Q000276:immunology / Q000628:therapy*; D001402:B-Lymphocytes / Q000276:immunology; D024043:Collagen Type II / Q000008:administration & dosage* / Q000276:immunology; D016207:Cytokines / Q000097:blood; D005434:Flow Cytometry; D015316:Genetic Therapy; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000906:Antibodies; D000941:Antigens; D024043:Collagen Type II; D016207:Cytokines