Silverman E D, Somma C, Khan M M, Melmon K L, Engleman E G
Department of Pediatrics, University of Toronto, Hospital for Sick Children, Ontario, Canada.
Arthritis Rheum. 1990 Feb;33(2):205-11. doi: 10.1002/art.1780330208.
The purpose of this study was to analyze T suppressor cell function in juvenile rheumatoid arthritis (JRA). JRA is a chronic inflammatory childhood disease of unknown etiology that is characterized by arthritis and immunoregulatory abnormalities. T suppressor cell precursors (CD8+, CD28-) were purified from the peripheral blood of 24 JRA patients, using a combination of monoclonal antibodies. These cells were treated with histamine or concanavalin A, agents that are known to induce suppressor activity. They were also tested for their ability to inhibit the proliferative response of autologous T cells to phytohemagglutinin. In some experiments, the accumulation of intracellular cAMP following histamine treatment was also measured. Twelve of 13 patients with clinically active JRA showed abnormal histamine-inducible T suppressor cell function, characterized by the failure of CD8+, CD28- T cells to mediate any detectable suppression. The failure of these cells to accumulate intracellular cAMP after histamine treatment was observed in 5 of 5 patients tested who had active disease. In contrast, 11 of 11 patients with clinically inactive JRA, 5 of 5 patients with cystic fibrosis, and 9 of 9 pediatric control subjects had normal histamine- and concanavalin A-inducible T suppressor cell function, and a normal cAMP response to histamine. These results suggest that patients with clinically active JRA have a reversible defect in T suppressor cell function that is associated with a failure of T suppressor cell precursors to accumulate intracellular cAMP following their exposure to selected immune stimuli.
本研究的目的是分析青少年类风湿性关节炎（JRA）中抑制性T细胞的功能。JRA是一种病因不明的儿童慢性炎症性疾病，其特征为关节炎和免疫调节异常。使用单克隆抗体组合从24例JRA患者的外周血中纯化出抑制性T细胞前体（CD8 +，CD28 -）。用组胺或伴刀豆球蛋白A处理这些细胞，已知这些试剂可诱导抑制活性。还测试了它们抑制自体T细胞对植物血凝素增殖反应的能力。在一些实验中，还测量了组胺处理后细胞内cAMP的积累。13例临床活动期JRA患者中有12例显示组胺诱导的抑制性T细胞功能异常，其特征为CD8 +，CD28 - T细胞未能介导任何可检测到的抑制作用。在5例测试的患有活动性疾病的患者中，观察到这些细胞在组胺处理后未能积累细胞内cAMP。相比之下，11例临床非活动期JRA患者、5例囊性纤维化患者和9例儿科对照受试者的组胺和伴刀豆球蛋白A诱导的抑制性T细胞功能正常，对组胺的cAMP反应也正常。这些结果表明，临床活动期JRA患者的抑制性T细胞功能存在可逆性缺陷，这与抑制性T细胞前体在暴露于特定免疫刺激后未能积累细胞内cAMP有关。
