Buzás E I, Mikecz K, Brennan F R, Glant T T
Department of Biochemistry, Rush Medical University, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612.
Cell Immunol. 1994 Oct 15;158(2):292-304. doi: 10.1006/cimm.1994.1277.
Proteoglycan (aggrecan)-induced arthritis is an autoimmune inflammatory animal model produced in genetically susceptible BALB/c mice. This animal model shows many similarities to human rheumatoid arthritis as indicated by clinical assessments, histopathological studies, and immunological parameters. The systemic immunization of mice with a select group of cartilage proteoglycans provokes immune responses to the immunizing antigen and then the production of cross-reactive antibodies to self proteoglycans. This is followed by an explosive proliferation of autoreactive T cells, especially in joint draining lymph nodes, accompanied by local (joint) inflammatory events. In the current experiments we found that lymphocytes from arthritic, or potentially arthritic but yet clinically asymptomatic animals, produced more IL-2 than those T cells obtained from animals immunized with nonarthritogenic PGs. In addition, synoviocytes isolated from prearthritic or arthritic animals produced several-fold more interleukin-1 beta (IL-1 beta) than cells from normal animals. Flow cytometric analysis indicated an autoantigen (mouse PG)-specific selective proliferation of surface Ig+/CD45R+ cells in prearthritic stages followed by the proliferation of predominantly T helper (CD4+) cells during and after the development of arthritis.
蛋白聚糖（聚集蛋白聚糖）诱导的关节炎是在基因易感的BALB/c小鼠中产生的一种自身免疫性炎症动物模型。如临床评估、组织病理学研究和免疫学参数所示，该动物模型与人类类风湿性关节炎有许多相似之处。用一组特定的软骨蛋白聚糖对小鼠进行全身免疫会引发对免疫抗原的免疫反应，进而产生针对自身蛋白聚糖的交叉反应抗体。随后，自身反应性T细胞会爆发性增殖，尤其是在关节引流淋巴结中，并伴有局部（关节）炎症事件。在当前实验中，我们发现来自患有关节炎或可能患有关节炎但临床上无症状动物的淋巴细胞产生的白细胞介素-2比那些用非致关节炎性蛋白聚糖免疫的动物获得的T细胞更多。此外，从关节炎前期或患有关节炎动物分离的滑膜细胞产生的白细胞介素-1β（IL-1β）比正常动物的细胞多几倍。流式细胞术分析表明，在关节炎前期阶段，自身抗原（小鼠蛋白聚糖）特异性的表面Ig+/CD45R+细胞选择性增殖，随后在关节炎发展期间及之后主要是辅助性T（CD4+）细胞增殖。
