Trentham D E, Townes A S, Kang A H, David J R
J Clin Invest. 1978 Jan;61(1):89-96. doi: 10.1172/JCI108929.
We have recently described a new animal model of arthritis induced by intradermal injection of a distinct type of collagen found in cartilage (type II collagen). Since immunologic sensitivity to collagen could play a role in the pathogenesis of this type II collagen-induced arthritis in rats, the ability of purified types of native collagens to induce cellular and humoral responses was quantified by antigeninduced tritiated thymidine incorporation into lymphocytes by collagen and passive hemagglutination, respectively. Rats injected intradermally with native heterologous or homologous type II collagens in adjuvant developed type-specific cellular as well as humoral reactivity. Types I and III collagens were less immunogenic than was type II. The latter collagen induced brisk cellular and humoral responses that were equivalent whether complete Freund's adjuvant or incomplete Freund's adjuvant were employed. Both responses could be induced by native type II collagens modified by limited pepsin digestion, indicating that they are not attributable to determinants in the telopeptide regions of the molecule. Thus, these studies demonstrate the unique immunogenic as well as arthritogenic properties of the type II collagen molecule and indicate that both result from a helical conformation of its structurally distinct alpha-chains. Further, they suggest that type II collagen may, by humoral or cellular mechanisms, provoke or perpetuate inflammation in other arthritic diseases.
我们最近描述了一种新的关节炎动物模型，该模型是通过皮内注射软骨中发现的一种独特类型的胶原蛋白（II型胶原蛋白）诱导而成。由于对胶原蛋白的免疫敏感性可能在大鼠这种II型胶原蛋白诱导的关节炎发病机制中起作用，因此分别通过胶原蛋白诱导的淋巴细胞中氚标记胸腺嘧啶核苷掺入和被动血凝反应，对纯化的天然胶原蛋白诱导细胞和体液反应的能力进行了定量。在佐剂中皮内注射天然异源或同源II型胶原蛋白的大鼠产生了型特异性细胞和体液反应性。I型和III型胶原蛋白的免疫原性低于II型。后一种胶原蛋白诱导了强烈的细胞和体液反应，无论使用完全弗氏佐剂还是不完全弗氏佐剂，反应都是等效的。有限胃蛋白酶消化修饰的天然II型胶原蛋白均可诱导这两种反应，表明它们并非归因于分子端肽区域中的决定簇。因此，这些研究证明了II型胶原蛋白分子独特的免疫原性和致关节炎特性，并表明两者均源于其结构独特的α链的螺旋构象。此外，它们表明II型胶原蛋白可能通过体液或细胞机制在其他关节炎疾病中引发或使炎症持续存在。
