Abnormal T suppressor cell function in juvenile rheumatoid arthritis.
Abnormal T suppressor cell function in juvenile rheumatoid arthritis.
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幼年类风湿性关节炎中 T 抑制细胞功能异常。
DOI：
10.1002/art.1780330208
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发表时间：
1990
影响因子：
--
通讯作者：
Engleman,EG
中科院分区：
文献类型：
--
作者：
Silverman,ED;Somma,C;Khan,MM;Melmon,KL;Engleman,EG
本研究的目的是分析幼年类风湿性关节炎 (JRA) 中 T 抑制细胞的功能。 JRA 是一种病因不明的慢性炎症性儿童疾病，其特征是关节炎和免疫调节异常。使用单克隆抗体组合从 24 名 JRA 患者的外周血中纯化 T 抑制细胞前体（CD8+、CD28−）。这些细胞用组胺或刀豆球蛋白 A 处理，这些药物已知可诱导抑制活性。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 名临床活动性 JRA 患者中有 12 名表现出异常的组胺诱导 T 抑制细胞功能，其特征是 CD8+、CD28− T 细胞无法介导任何可检测到的抑制。在接受组胺治疗的 5 名患有活动性疾病的患者中，有 5 名观察到这些细胞在组胺治疗后未能积聚细胞内 cAMP。相比之下，11 名临床非活动性 JRA 患者中的 11 名、5 名囊性纤维化患者中的 5 名以及 9 名儿科对照受试者中的 9 名具有正常的组胺和刀豆蛋白 A 诱导 T 抑制细胞功能，以及对组胺的正常 cAMP 反应。这些结果表明，临床活动性 JRA 患者的 T 抑制细胞功能存在可逆性缺陷，这与 T 抑制细胞前体在暴露于选定的免疫刺激后未能积累细胞内 cAMP 相关。
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.