Gilman S C, Daniels J F, Wilson R E, Carlson R P, Lewis A J
Ann Rheum Dis. 1984 Dec;43(6):847-55. doi: 10.1136/ard.43.6.847.
Lewis rats injected in the hind paw with Mycobacterium butyricum develop a severe polyarthritis which shares certain features in common with rheumatoid arthritis in man. Spleen and peripheral blood mononuclear cells from rats with this form of arthritic disease proliferate poorly in vitro in response to concanavalin A (con A), phytohaemagglutinin (PHA), and pokeweed mitogen (PWM). The splenic hyporesponsiveness appears within four days of M. butyricum injection (three to five days prior to the development of detectable arthritis), reaches a peak 16-22 days following injection, and persists for at least 40 days. Buffalo strain rats injected with M. butyricum do not develop arthritis, and their spleen cells respond normally to con A, PHA, and PWM. In response to lipopolysaccharide (LPS) the synthesis of interleukin 1 (IL-1) by spleen or peritoneal macrophages from arthritic Lewis rats equalled or exceeded that of macrophages from normal rats. In contrast splenic T cells from arthritic rats produced reduced amounts of interleukin 2 (IL-2; T cell growth factor) in response to stimulation with PHA or con A. Moreover, con-A-activated spleen cells from arthritic rats failed to bind IL-2 and to respond to this growth factor with increased 3H-TdR uptake as did normal spleen cells. In-vitro treatment of 'arthritic' cells with 10(-5) M indomethacin did not restore to normal their reduced mitogen responsiveness, and spleen cells from normal and arthritic rats were equally sensitive to the inhibitory effects of prostaglandin E2 on con-A-induced proliferative responses. These results indicate that peripheral lymphoid function is compromised in rats with adjuvant-induced arthritis and that this functional deficit is mediated by aberrant synthesis of and response to IL-2 by T cells of arthritic animals.
给后爪注射丁酸分枝杆菌的Lewis大鼠会患上严重的多关节炎，这种关节炎与人的类风湿性关节炎有某些共同特征。患有这种关节炎疾病的大鼠的脾脏和外周血单核细胞，在体外对刀豆球蛋白A（Con A）、植物血凝素（PHA）和商陆有丝分裂原（PWM）的反应增殖能力较差。脾脏反应低下在注射丁酸分枝杆菌后的四天内出现（在可检测到关节炎出现前的三到五天），在注射后16 - 22天达到峰值，并持续至少40天。注射丁酸分枝杆菌的布法罗品系大鼠不会患关节炎，其脾细胞对Con A、PHA和PWM的反应正常。对脂多糖（LPS）的反应中，来自患有关节炎的Lewis大鼠的脾脏或腹腔巨噬细胞产生白细胞介素1（IL - 1）的量等于或超过正常大鼠巨噬细胞产生的量。相比之下，患有关节炎的大鼠的脾脏T细胞在受到PHA或Con A刺激时产生的白细胞介素2（IL - 2；T细胞生长因子）量减少。此外，来自患有关节炎大鼠的Con - A激活的脾细胞不像正常脾细胞那样能结合IL - 2并对这种生长因子产生3H - TdR摄取增加的反应。用10(-5) M消炎痛对“关节炎”细胞进行体外处理，不能使其降低的有丝分裂原反应恢复正常，正常和患有关节炎大鼠的脾细胞对前列腺素E2对Con - A诱导的增殖反应的抑制作用同样敏感。这些结果表明，佐剂诱导性关节炎大鼠的外周淋巴功能受损，并且这种功能缺陷是由关节炎动物T细胞对IL - 2的异常合成和反应介导的。
