Müssener A, Lorentzen J C, Kleinau S, Klareskog L
Department of Rheumatology, Karolinska Hospital, Stockholm, Sweden.
Eur J Immunol. 1997 Mar;27(3):695-9. doi: 10.1002/eji.1830270318.
Collagen-induced arthritis (CIA) is a T cell-dependent disease in which susceptibility is controlled by genes both within and outside the major histocompatibility complex (MHC). In the present study, we compared the humoral responses and kinetics of cytokine secretion patterns in the draining lymph nodes of arthritis-susceptible DA rats and arthritis-resistant F344 and DA MHC congenic PVG.1AV1 rats immunized with rat type II collagen (RCII) in incomplete Freund's adjuvant. The results demonstrate a marked humoral RCII response and a Th1 cytokine profile, with expression of interferon-gamma and interleukin (IL)-2 mRNA in DA rats; a limited humoral RCII response and a Th2 cytokine profile, with expression of IL-4 mRNA in arthritis-resistant F344 rats; and a marked humoral RCII response in arthritis-resistant PVG.1AV1 rats. However, in contrast to DA rats, PVG.1AV1 rats produce IgG1 autoantibodies which, together with strong expression of IL-4 mRNA, indicates the involvement of Th2 subsets. From these data, we conclude that non-MHC gene(s) determines the direction of the anti-RCII response towards a Th1 disease-promoting, or a Th2 disease-limiting response.
胶原诱导性关节炎（CIA）是一种T细胞依赖性疾病，其易感性由主要组织相容性复合体（MHC）内外的基因控制。在本研究中，我们比较了用不完全弗氏佐剂免疫大鼠II型胶原（RCII）的关节炎易感DA大鼠、关节炎抗性F344大鼠和DA MHC同基因PVG.1AV1大鼠引流淋巴结中的体液反应和细胞因子分泌模式的动力学。结果显示，DA大鼠有明显的体液RCII反应和Th1细胞因子谱，伴有干扰素-γ和白细胞介素（IL）-2 mRNA表达；关节炎抗性F344大鼠的体液RCII反应有限且有Th2细胞因子谱，伴有IL-4 mRNA表达；关节炎抗性PVG.1AV1大鼠有明显的体液RCII反应。然而，与DA大鼠不同，PVG.1AV1大鼠产生IgG1自身抗体，这与IL-4 mRNA的强烈表达一起表明Th2亚群的参与。从这些数据中，我们得出结论，非MHC基因决定了抗RCII反应朝着促进疾病的Th1反应或限制疾病的Th2反应的方向发展。
