Journal
JOURNAL OF IMMUNOLOGY
Volume 190, Issue 4, Pages 1457-1465Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1201517
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Funding
- NIAMS NIH HHS [R01 AR051749] Funding Source: Medline
- NIDDK NIH HHS [R01 DK081166] Funding Source: Medline
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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. The Journal of Immunology, 2013, 190: 1457-1465.
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