Kouskoff V, Korganow A S, Duchatelle V, Degott C, Benoist C, Mathis D
Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP), Illkirch, France.
Cell. 1996 Nov 29;87(5):811-22. doi: 10.1016/s0092-8674(00)81989-3.
Rheumatoid arthritis (RA) is a chronic joint disease characterized by leukocyte invasion and synoviocyte activation followed by cartilage and bone destruction. Its etiology and pathogenesis are poorly understood. We describe a spontaneous mouse model of this syndrome, generated fortuitously by crossing a T cell receptor (TCR) transgenic line with the NOD strain. All offspring develop a joint disease highly reminiscent of RA in man. The trigger for the murine disorder is chance recognition of a NOD-derived major histocompatibility complex (MHC) class II molecule by the transgenic TCR; progression to arthritis involves CD4+ T, B, and probably myeloid cells. Thus, a joint-specific disease need not arise from response to a joint-specific antigen but can be precipitated by a breakdown in general mechanisms of self-tolerance resulting in systemic self-reactivity. We suggest that human RA develops by an analogous mechanism.
类风湿性关节炎（RA）是一种慢性关节疾病，其特征是白细胞浸润和滑膜细胞活化，随后导致软骨和骨破坏。其病因和发病机制尚不清楚。我们描述了一种该综合征的自发小鼠模型，它是通过将一个T细胞受体（TCR）转基因品系与NOD品系偶然杂交产生的。所有后代都会患上一种与人类RA极为相似的关节疾病。引发小鼠疾病的原因是转基因TCR偶然识别了一种源自NOD的主要组织相容性复合体（MHC）II类分子；关节炎的发展涉及CD4 + T细胞、B细胞，可能还有髓样细胞。因此，关节特异性疾病不一定源于对关节特异性抗原的反应，而是可能由自身耐受性的一般机制崩溃导致全身自身反应性而引发。我们认为人类RA是通过类似机制发展而来的。
