A citrullinated fibrinogen-specific T cell line enhances autoimmune arthritis in a mouse model of rheumatoid arthritis.
A citrullinated fibrinogen-specific T cell line enhances autoimmune arthritis in a mouse model of rheumatoid arthritis.
复制标题
DOI：
10.4049/jimmunol.1201517
复制
发表时间：
2013-02-15
期刊：
影响因子：
--
通讯作者：
Holers VM
中科院分区：
文献类型：
--
作者：
Cordova KN;Willis VC;Haskins K;Holers VM
瓜氨酸蛋白源自肽基精氨酸转化为肽基瓜氨酸，存在于类风湿性关节炎 (RA) 患者的关节中，这些患者还独特地产生高水平的抗瓜氨酸蛋白抗体。瓜氨酸纤维蛋白原（CF）在类风湿滑膜组织中含量丰富，抗瓜氨酸蛋白抗体阳性的RA患者表现出含有CF的循环免疫复合物。因此，CF 是 RA 致病性自身免疫的潜在主要靶标。据信，T 细胞通过启动、控制和驱动 RA 中的 Ag 特异性免疫反应来参与这一过程。在这项研究中，我们分离出了一种针对 CF 的 CD4 T 细胞系，它能产生炎症细胞因子。当将这种 T 细胞系转移到患有胶原诱导关节炎 (CIA) 的小鼠体内时，它会特别增强自身免疫性关节炎的严重程度。此外，在 CIA 中接受 T 细胞的小鼠中，针对小鼠 II 型胶原的致病性 IgG2a 自身抗体水平增加，并且滑膜中这些 T 细胞的水平增加，表明 T 细胞可能对 B 细胞反应产生全身影响，并对炎症环境产生局部影响。这项工作表明，CF 特异性 CD4 T 细胞可以在 CIA 发病后加剧疾病的严重程度。
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.
登录
查看更多内容
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
82.9
作者：
Korn, Thomas;Reddy, Jayagopala;Kuchroo, Vijay K.
通讯作者：
Kuchroo, Vijay K.
影响因子：
4.9
作者：
Kinloch, Andrew;Tatzer, Verena;Wait, Robin;Peston, David;Lundberg, Karin;Donatien, Phillipe;Moyes, David;Taylor, Peter C;Venables, Patrick J
通讯作者：
Venables, Patrick J
影响因子：
4.9
作者：
Angyal, Adrienn;Egelston, Colt;Mikecz, Katalin
通讯作者：
Mikecz, Katalin
影响因子：
4.4
作者：
Chapuy-Regaud, S;Sebbag, M;Serre, G
通讯作者：
Serre, G