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.