Gene Therapy Induces Antigen-Specific Tolerance in Experimental Collagen-Induced Arthritis

• Published in: PloS one Vol. 11; no. 5; p. e0154630
• Main Authors: Tengvall, Sara, Eneljung, Tove, Jirholt, Pernilla, Turesson, Olof, Wing, Kajsa, Holmdahl, Rikard, Kihlberg, Jan, Stern, Anna, Mårtensson, Inga-Lill, Henningsson, Louise, Gustafsson, Kenth, Gjertsson, Inger
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.05.2016; Public Library of Science (PLoS)
• Subjects: Amino acids; Analysis; Animals; Antibodies - immunology; Antigen-presenting cells; Antigens; Antigens - immunology; Arthritis; Arthritis, Experimental - blood; Arthritis, Experimental - immunology; Arthritis, Experimental - therapy; AUTOIMMUNE ARTHRITIS; Autoimmune diseases; B-CELLS; B-Lymphocytes - immunology; Biochemistry; Biology and Life Sciences; Biophysics; Care and treatment; Collagen; Collagen (type II); Collagen Type II - administration & dosage; Collagen Type II - immunology; Cytokines; Cytokines - blood; DENDRITIC CELLS; Dosage and administration; Drug tolerance; Flow Cytometry; Gene expression; Gene therapy; Genetic Therapy; Health aspects; II COLLAGEN; Immune system; Immune Tolerance; IMMUNE-RESPONSES; Immunization; Immunoglobulins; Immunological tolerance; Immunology; Immunosuppressive agents; INDUCTION; Inflammation; Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Medicin och hälsovetenskap; Medicine and Health Sciences; Mice; Mice, Inbred DBA; Pathogenesis; Peptides; Proteins; REGULATORY T-CELLS; Research and Analysis Methods; Reumatologi och inflammation; Rheumatoid arthritis; Rheumatology; Rheumatology and Autoimmunity; Risk factors; Rodents; SELF-TOLERANCE; Signaling; Studies; SUPPRESSION; Suppressors; T-Lymphocytes - immunology; TRANSGENIC MICE; Transplants & implants; Sweden
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0154630

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.