Role of Citrullinated Fibrinogen Peptides in the Activation of CD4 T Cells from Patients with Rheumatoid Arthritis.
- Author:
Kihyuk SHIN
1
;
Seokchan HONG
;
Eun Hye CHOI
;
Mi Kyoung LIM
;
Seung Cheol SHIM
;
Ji Hyeon JU
;
Seung Hyo LEE
Author Information
- Publication Type:Original Article
- Keywords: Rheumatoid arthritis (RA); Citrullinated fibrinogen (cFBG); CD4 T cell; HLA-DR4; Interferon-gamma(IFN-gamma); Interleukin-17A (IL-17A)
- MeSH: Animals; Arthritis, Rheumatoid; Candida albicans; Cytokines; Epitopes, T-Lymphocyte; Fibrinogen; HLA-DR4 Antigen; Humans; Interleukin-17; Mice; Mice, Transgenic; Mycobacterium tuberculosis; Peptides; T-Lymphocytes; Tetanus Toxoid
- From:Immune Network 2013;13(4):116-122
- CountryRepublic of Korea
- Language:English
- 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-gamma(IFN-gamma) and interleukin-17A (IL-17A), were measured. In addition, CD4 T cells from RA patients were stimulated with the citrullinated fibrinogen peptide, Fib-alpha 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-gamma 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.