title: A citrullinated fibrinogen-specific T cell line enhances autoimmune arthritis in a mouse model of rheumatoid arthritis.
abstract: Citrullinated proteins, derived from the conversion of peptidyl-arginine to peptidyl-citrulline, are present in the joints of patients with rheumatoid arthritis (RA), who also uniquely produce high levels of anti-citrullinated protein Abs. Citrullinated fibrinogen (CF) is abundant in rheumatoid synovial tissue, and anti-citrullinated protein Ab-positive RA patients exhibit circulating immune complexes containing CF. Thus, CF is a potential major target of pathogenic autoimmunity in RA. T cells are believed to be involved in this process by initiating, controlling, and driving Ag-specific immune responses in RA. In this study, we isolated a CD4 T cell line specific for CF that produces inflammatory cytokines. When transferred into mice with collagen-induced arthritis (CIA), this T cell line specifically enhanced the severity of autoimmune arthritis. Additionally, pathogenic IgG2a autoantibody levels to mouse type II collagen were increased in mice that received the T cells in CIA, and levels of these T cells were increased in the synovium, suggesting the T cells may have had systemic effects on the B cell response as well as local effects on the inflammatory environment. This work demonstrates that CD4 T cells specific for CF can amplify disease severity after onset of CIA.
authors: Division of Rheumatology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors: Kristen N
authors: KN
authors: Cordova
authors: Van C
authors: VC
authors: Willis
authors: Kathryn
authors: K
authors: Haskins
authors: V Michael
authors: VM
authors: Holers
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D001323:Autoantibodies / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D002478:Cells, Cultured; D002956:Citrulline / Q000378:metabolism*; D003094:Collagen / Q000633:toxicity; D024043:Collagen Type II / Q000276:immunology / Q000633:toxicity; D005340:Fibrinogen / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D015854:Up-Regulation / Q000276:immunology
chemical_list: D001323:Autoantibodies; D024043:Collagen Type II; D002956:Citrulline; D005340:Fibrinogen; D003094:Collagen