Osman G E, Cheunsuk S, Allen S E, Chi E, Liggitt H D, Hood L E, Ladiges W C
Department of Molecular Biotechnology, University of Washington School of Medicine, Seattle 98195, USA.
Int Immunol. 1998 Nov;10(11):1613-22. doi: 10.1093/intimm/10.11.1613.
Animal models of autoimmune diseases have been instrumental in advancing our understanding of autoimmunity in humans. Collagen-induced arthritis in mice is an autoimmune disease model of rheumatoid arthritis, which is MHC class II restricted and CD4 T cell dependent. To better understand the fundamental role of T cells in arthritis, we have generated a transgenic mouse carrying the rearranged Valpha11.1 and Vbeta8.2 TCR chain genes isolated from a type II collagen (CII)-specific T cell hybridoma. Cell surface analysis indicated that Vbeta8.2 chain was expressed on the surface of nearly all peripheral T cells. Analysis of T cell subsets in transgenic mice revealed a profound skewing in peripheral T cells towards the CD4 population. Although peripheral T cells were not tolerant to CII and responded to CII stimulation in vitro, transgenic mice did not develop spontaneous arthritis. However, a rapid onset of arthritis with severe clinical signs was detected in transgenic mice after immunization with CII in complete Freund's adjuvant. Histological analysis of inflamed joints showed a great resemblance to arthritic joints in man. This unique transgenic mouse model provides valuable insights into the mechanism of arthritis and into potential specific immune interventions.
自身免疫性疾病的动物模型在促进我们对人类自身免疫的理解方面发挥了重要作用。小鼠胶原诱导性关节炎是类风湿性关节炎的一种自身免疫性疾病模型，它受MHC II类分子限制且依赖CD4 T细胞。为了更好地理解T细胞在关节炎中的基本作用，我们构建了一种转基因小鼠，其携带从II型胶原（CII）特异性T细胞杂交瘤中分离出的重排的Valpha11.1和Vbeta8.2 TCR链基因。细胞表面分析表明，几乎所有外周T细胞表面都表达Vbeta8.2链。对转基因小鼠T细胞亚群的分析显示，外周T细胞明显偏向CD4群体。尽管外周T细胞对CII不耐受且在体外对CII刺激有反应，但转基因小鼠并未发生自发性关节炎。然而，在用完全弗氏佐剂免疫CII后，转基因小鼠出现了伴有严重临床症状的快速关节炎发作。对发炎关节的组织学分析显示与人的关节炎关节非常相似。这种独特的转基因小鼠模型为关节炎的发病机制和潜在的特异性免疫干预提供了有价值的见解。
