Wang Y, Kristan J, Hao L, Lenkoski C S, Shen Y, Matis L A
Alexion Pharmaceuticals, Inc., New Haven, CT 06511; and Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
J Immunol. 2000 Apr 15;164(8):4340-7. doi: 10.4049/jimmunol.164.8.4340.
Collagen-induced arthritis (CIA) represents an animal model of autoimmune polyarthritis with significant similarities to human rheumatoid arthritis that can be induced upon immunization with native type II collagen. As in rheumatoid arthritis, both cellular and humoral immune mechanisms contribute to disease pathogenesis. Genotypic studies have identified at least six genetic loci contributing to arthritis susceptibility, including the class II MHC. We have examined the mechanism of Ab-mediated inflammation in CIA joints, specifically the role of complement activation, by deriving a line of mice from the highly CIA-susceptible DBA/1LacJ strain that are congenic for deficiency of the C5 complement component. We show that such C5-deficient DBA/1LacJ animals mount normal cellular and humoral immune responses to native type II collagen, with the activation of collagen-specific TNF-alpha-producing T cells in the periphery and substantial intra-articular deposition of complement-fixing IgG Abs. Nevertheless, these C5-deficient mice are highly resistant to the induction of CIA. These data provide evidence for an important role of complement in Ab-triggered inflammation and in the pathogenesis of autoimmune arthritis.
胶原诱导的关节炎（CIA）是一种自身免疫性多关节炎动物模型，与人类类风湿关节炎有显著相似之处，可通过用天然II型胶原免疫诱导产生。与类风湿关节炎一样，细胞免疫和体液免疫机制均参与疾病发病过程。基因研究已确定至少六个与关节炎易感性相关的基因位点，包括II类主要组织相容性复合体（MHC）。我们通过从高度易患CIA的DBA/1LacJ品系培育出一组C5补体成分缺陷的同源小鼠，研究了CIA关节中抗体介导的炎症机制，特别是补体激活的作用。我们发现，此类C5缺陷的DBA/1LacJ动物对天然II型胶原产生正常的细胞免疫和体液免疫反应，外周血中胶原特异性产生肿瘤坏死因子-α（TNF-α）的T细胞被激活，关节内有大量固定补体的IgG抗体沉积。然而，这些C5缺陷小鼠对CIA的诱导具有高度抗性。这些数据证明补体在抗体触发的炎症以及自身免疫性关节炎发病机制中起重要作用。
