van den Broek M F, van Bruggen M C, Koopman J P, Hazenberg M P, van den Berg W B
Department of Rheumatic Diseases, University Hospital Nijmegen, The Netherlands.
Clin Exp Immunol. 1992 May;88(2):313-7. doi: 10.1111/j.1365-2249.1992.tb03079.x.
Streptococcal cell wall (SCW)-induced arthritis is a chronic, erosive polyarthritis that can be induced in susceptible Lewis rats by one i.p. injection of an aqueous, sterile suspension of SCW. F344 rats are resistant to chronic joint inflammation. Our previous studies showed a correlation between susceptibility to SCW-induced arthritis and the ability to mount SCW-specific T cell responses, suggesting tolerance to SCW as a putative mechanism. Here we prevented the induction of tolerance to bacterial epitopes in F344 rats by using them germ-free and analysed susceptibility to arthritis subsequently. In addition, we conventionalized germ-free F344 rats at different times before induction of arthritis. Our results show that germ-free F344 rats are susceptible to SCW-induced arthritis with a similar severity, chronicity, incidence and onset as Lewis rats. Moreover, T cells isolated from germ-free F344 rats were able to respond to SCW. Conventionalization dramatically moderates arthritis and makes T cells unresponsive to SCW again. Thus, in normal rats (F344) a state of tolerance to arthritogenic epitopes is induced (neonatally) and maintained through life by the bacterial flora, resulting in resistance to bacterium-induced arthritides. In arthritis-prone (Lewis) rats, this tolerance is deficient and/or easily broken.
链球菌细胞壁（SCW）诱导的关节炎是一种慢性侵蚀性多关节炎，通过腹腔注射一次无菌的SCW水性悬浮液可在易感的Lewis大鼠中诱发。F344大鼠对慢性关节炎症具有抗性。我们之前的研究表明，对SCW诱导的关节炎的易感性与产生SCW特异性T细胞反应的能力之间存在相关性，提示对SCW的耐受性是一种可能的机制。在此，我们通过将F344大鼠饲养在无菌环境中来防止其对细菌表位产生耐受性，随后分析其对关节炎的易感性。此外，我们在诱导关节炎之前的不同时间将无菌F344大鼠进行常规饲养。我们的结果表明，无菌F344大鼠对SCW诱导的关节炎易感，其严重程度、慢性程度、发病率和发病时间与Lewis大鼠相似。此外，从无菌F344大鼠分离的T细胞能够对SCW作出反应。常规饲养显著减轻了关节炎，并使T细胞再次对SCW无反应。因此，在正常大鼠（F344）中，（在新生期）诱导了对致关节炎表位的耐受状态，并通过细菌菌群终生维持，从而使其对细菌诱导的关节炎具有抗性。在易患关节炎的（Lewis）大鼠中，这种耐受性不足和/或容易被打破。
