van den Broek M F, van Bruggen M C, Stimpson S A, Severijnen A J, van de Putte L B, van den Berg W B
Department of Rheumatology, University Hospital Nijmegen, The Netherlands.
Clin Exp Immunol. 1990 Feb;79(2):297-306. doi: 10.1111/j.1365-2249.1990.tb05194.x.
One i.p. injection of a sterile suspension of streptococcal cell walls (SCW) induces chronic erosive polyarthritis in susceptible Lewis rats, but not in resistant F344 or nude Lewis rats. Because continuous exacerbations may be one possible mechanism underlying chronic disease, we studied the mechanism of these flare-up reactions in Lewis and F344 rats. Injection of SCW into the right knee joint of rats induced a transient monoarthritis in both strains. Reactivation of the subsided arthritis by i.v. administration of the same antigen could be evoked only in the Lewis rat. Even repeated i.v. challenges with SCW failed to induce a flare-up reaction in the F344 rat, while the Lewis rat went through an exacerbation after every challenge. Removal of T lymphocytes by monoclonal antibodies before induction of an exacerbation rendered Lewis rats refractory to flare-up reactions, thus indicating the T cell-dependence of this reaction. Furthermore, when cell walls from heterologous bacteria were tested for their capacity to induce exacerbations of SCW-induced monoarthritis and to induce proliferation of SCW-specific T lymphocytes in vitro, a strong correlation between both features was found, again pointing to a role for SCW-specific T cells in exacerbations. Together, these data support our hypothesis that chronic arthritis is the result from repeated reactivations of a waning arthritis which are dependent on antigen-specific T lymphocytes.
一次腹腔注射链球菌细胞壁(SCW)无菌悬液可在易感性Lewis大鼠中诱发慢性侵蚀性多关节炎,但在抗性F344大鼠或裸Lewis大鼠中则不会诱发。由于持续加重可能是慢性病潜在的一种机制,我们研究了Lewis大鼠和F344大鼠中这些发作反应的机制。向大鼠右膝关节注射SCW在两种品系中均诱发了短暂的单关节炎。仅在Lewis大鼠中,通过静脉注射相同抗原来激活消退的关节炎。即使反复静脉注射SCW也未能在F344大鼠中诱发发作反应,而Lewis大鼠每次受到刺激后都会病情加重。在诱发病情加重之前,用单克隆抗体清除T淋巴细胞使Lewis大鼠对发作反应产生抗性,从而表明该反应依赖于T细胞。此外,当测试来自异源细菌的细胞壁诱导SCW诱导的单关节炎加重以及在体外诱导SCW特异性T淋巴细胞增殖的能力时,发现这两个特征之间存在很强的相关性,再次表明SCW特异性T细胞在病情加重中起作用。总之,这些数据支持了我们的假设,即慢性关节炎是由逐渐消退的关节炎反复激活所致,而这种激活依赖于抗原特异性T淋巴细胞。