Kim Eugene Y, Chi Howard H, Bouziane Mohammed, Gaur Amitabh, Moudgil Kamal D
Department of Microbiology and Immunology, University of Maryland School of Medicine, HH 323C, 660 W. Redwood St., Baltimore, MD 21201, USA.
Clin Immunol. 2008 Apr;127(1):98-106. doi: 10.1016/j.clim.2008.01.003. Epub 2008 Feb 13.
The pathogenesis of T cell-mediated diseases like rheumatoid arthritis (RA) has typically been explained in the context of the Th1-Th2 paradigm: the initiation/propagation by pro-inflammatory cytokines, and downregulation by Th2 cytokines. However, in our study based on the adjuvant-induced arthritis (AA) model of RA, we observed that Lewis (LEW) (RT.1(l)) rats at the recovery phase of AA showed the highest level of IFN-gamma in recall response to mycobacterial heat-shock protein 65 (Bhsp65), whereas AA-resistant Wistar-Kyoto (WKY) (RT.1(l)) rats secreted high levels of IFN-gamma much earlier following disease induction. However, no significant secretion of IL-10 or TGF-beta was observed in either strain. Furthermore, pre-treatment of LEW rats with a peptide of self (rat) hsp65 (R465), which induced T cells secreting predominantly IFN-gamma, afforded protection against AA and decreased IL-17 expression by the arthritogenic epitope-restimulated T cells. These results provide a novel perspective on the pathogenesis of autoimmune arthritis.
像类风湿性关节炎（RA）这样的T细胞介导疾病的发病机制通常是在Th1-Th2范式的背景下解释的：由促炎细胞因子引发/传播，并由Th2细胞因子下调。然而，在我们基于RA的佐剂诱导性关节炎（AA）模型的研究中，我们观察到处于AA恢复期的Lewis（LEW）（RT.1(l)）大鼠在对分枝杆菌热休克蛋白65（Bhsp65）的回忆反应中显示出最高水平的干扰素-γ，而对AA有抗性的Wistar-Kyoto（WKY）（RT.1(l)）大鼠在疾病诱导后更早分泌高水平的干扰素-γ。然而，在这两个品系中均未观察到白细胞介素-10或转化生长因子-β的显著分泌。此外，用自身（大鼠）热休克蛋白65（R465）的肽预处理LEW大鼠，该肽诱导T细胞主要分泌干扰素-γ，可提供针对AA的保护，并降低致关节炎表位再刺激的T细胞的白细胞介素-17表达。这些结果为自身免疫性关节炎的发病机制提供了新的视角。
