title: Role of citrullinated fibrinogen peptides in the activation of CD4 T cells from patients with rheumatoid arthritis.
abstract: This study was conducted to determine whether CD4 T cell responses to citrullinated fibrinogen occur in patients with rheumatoid arthritis (RA), especially in HLA-DR4-positive subjects. Whole peripheral blood mononuclear cells (PBMCs) of RA patients and control subjects were stimulated with citrullinated fibrinogen peptides, and T-cell production of proliferation and proinflammatory cytokines, such as interferon-γ(IFN-γ) and interleukin-17A (IL-17A), were measured. In addition, CD4 T cells from RA patients were stimulated with the citrullinated fibrinogen peptide, Fib-α R84Cit, identified as a DRB1(*)0401-restricted T cell epitope in HLA-DR4 transgenic mice, and the degree of T cell activation was examined similarly. No proliferative responses to the citrullinated fibrinogen peptides were observed in whole PBMCs or CD4 T cells from RA patients. Furthermore, no increased production of IFN-γ or IL-17A was found in whole PBMCs or CD4 T cells stimulated with the citrullinated fibrinogen peptides, although these cells responded to recall antigen, a mixture of tetanus toxoid, purified protein derivative (PPD) from Mycobacterium tuberculosis, and Candida albicans. The results of this study indicate that anti-citrulline immunity in RA patients may be mediated by fibrinogen because there is no evidence of CD4 T cell-mediated immune responses to citrullinated fibrinogen peptides.
authors.affiliation: Graduate School of Medical Science and Engineering, Biomedical Research Center, KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Kihyuk
authors.initials: K
authors.lastname: Shin
authors.forename: Seokchan
authors.initials: S
authors.lastname: Hong
authors.forename: Eun-Hye
authors.initials: EH
authors.lastname: Choi
authors.forename: Mi-Kyoung
authors.initials: MK
authors.lastname: Lim
authors.forename: Seung-Cheol
authors.initials: SC
authors.lastname: Shim
authors.forename: Ji-Hyeon
authors.initials: JH
authors.lastname: Ju
authors.forename: Seung-Hyo
authors.initials: SH
authors.lastname: Lee
keywords: CD4 T cell; Citrullinated fibrinogen (cFBG); HLA-DR4; Interferon-γ(IFN-γ); Interleukin-17A (IL-17A); Rheumatoid arthritis (RA)