Immunopathogenesis of collagen arthritis.
Collagen-induced arthritis (CIA) is an animal model of autoimmunity that has been studied extensively because of its similarities to rheumatoid arthritis (RA). CIA is induced in genetically susceptible strains of mice by immunization with type II collagen (CII), and both T cell and B cell immunity to CII are required for disease manifestation. Like RA, CIA is primarily an autoimmune disease of articular joints and susceptibility to CIA is linked to specific class II molecules of the major histocompatibility complex (H-2(r) and H-2(q)). Recently, it was demonstrated that transgenic expression of HLA-DR1 (*0101) or DR4 (*0401) molecules associated with susceptibility to RA also conferred susceptibility to CIA in the mouse model. The T cell response to CII has been extensively characterized in both the DR transgenic and naturally susceptible mouse strains, including the antigenic determinants recognized, the role of post transcriptional modifications of these determinants in the pathogenic T cell response, and the cytokines produced. Like most class II-mediated autoimmune diseases, the cytokine production of CII-specific T cells reflects a Th1 phenotype of the autoimmune response. While the direct role of T cells in the pathogenesis of CIA is unclear, the B cell response in terms of anti-CII immunoglobulin is critical to the development of the disease. This response, predominated by the IgG2 isotype, requires the activation of the complement cascade for the development of CIA. In recent years, the pathogenesis of this model has been studied extensively and the CIA model is proving to be a valuable asset for the design of new immunotherapeutics for the potential treatment of RA and other autoimmune diseases.
Brand
David D
DD
Veterans Affairs Medical Center, Research Service (151), 130 Jefferson Avenue, Memphis, TN 38104, USA.
Kang
Andrew H
AH
Rosloniec
Edward F
EF
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D024043:Collagen Type II / Q000276:immunology; D004195:Disease Models, Animal; D015804:HLA-DR4 Antigen / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology
D024043:Collagen Type II; D015804:HLA-DR4 Antigen