Matsubayashi S, Akasu F, Kasuga Y, Snow K, Keystone E, Volpé R
Endocrine Research Laboratory, Wellesley Hospital, University of Toronto, Ontario, Canada.
Clin Exp Immunol. 1990 Oct;82(1):63-8. doi: 10.1111/j.1365-2249.1990.tb05404.x.
The production of interferon-gamma (IFN-gamma) by peripheral blood mononuclear cells (PBMC), CD4 cells, or CD8 cells in response to interleukin-2 (IL-2) stimulation has been studied; the samples were obtained from 12 healthy control subjects, 19 patients with Graves' disease (10 hyperthyroid and nine euthyroid), 13 patients with Hashimoto's thyroiditis (four hypothyroid and nine euthyroid), and 15 patients with rheumatoid arthritis (11 active and four inactive). A dose of IL-2 (25 U/ml) was utilized to induce IFN-gamma by PBMC from all four groups. The incremental increase in IFN-gamma values (with IL-2 stimulation minus without stimulation) was significantly less in PBMC from patients with Graves' disease, Hashimoto's thyroiditis, and rheumatoid arthritis than that in PBMC from control subjects. The values from PBMC in patients with Graves' disease in a euthyroid state were below normal but greater than those from patients with Graves' disease in a hyperthyroid state. The incremental increase in IFN-gamma values from Graves' disease PBMC correlated with the serum TSH values (r = 0.622, P less than 0.01), but not with thyroid autoantibodies (anti-thyroid microsomal antibodies, anti-thyroid microsomal antibodies, nor TSH-binding inhibitory immunoglobulin activities). The incremental increase in IFN-gamma from PBMC from both control subjects and Graves' disease was correlated with that from CD4 cells (r = 0.711, P less than 0.01), but not with that from CD8 cells. The production of IFN-gamma in response to IL-2 from PBMC in Graves' disease correlated inversely with thyroid function, appearing to reflect the very effect of hyperthyroidism in this process. The precise explanation of these phenomena remains unclear. The decreased response of IFN-gamma to IL-2 stimulation by PBMC from patients with Graves' disease, Hashimoto's thyroiditis, and rheumatoid arthritis seems to be a non-specific phenomenon occurring in both organ specific autoimmune disease and systemic autoimmune disease. It may be due to a down-regulation in autoimmune disease of CD4 cells in response to IL-2, a decreased level of IL-2 cellular receptors or a decreased receptor affinity, associated increased soluble IL-2 receptors, or a defect of the intra-CD4 cellular IL-2 signal to produce or release IFN-gamma in the conditions studied.
研究了外周血单个核细胞（PBMC）、CD4细胞或CD8细胞在白细胞介素-2（IL-2）刺激下产生干扰素-γ（IFN-γ）的情况；样本取自12名健康对照者、19例格雷夫斯病患者（10例甲状腺功能亢进和9例甲状腺功能正常）、13例桥本甲状腺炎患者（4例甲状腺功能减退和9例甲状腺功能正常）以及15例类风湿关节炎患者（11例活动期和4例非活动期）。使用一定剂量的IL-2（25 U/ml）来诱导所有四组的PBMC产生IFN-γ。格雷夫斯病、桥本甲状腺炎和类风湿关节炎患者的PBMC中，IFN-γ值的增量增加（IL-2刺激后减去未刺激时）显著低于对照者的PBMC。甲状腺功能正常的格雷夫斯病患者PBMC的值低于正常，但高于甲状腺功能亢进的格雷夫斯病患者。格雷夫斯病PBMC中IFN-γ值的增量增加与血清促甲状腺激素（TSH）值相关（r = 0.622，P < 0.01），但与甲状腺自身抗体（抗甲状腺微粒体抗体、抗甲状腺微粒体抗体以及TSH结合抑制免疫球蛋白活性）无关。对照者和格雷夫斯病患者PBMC中IFN-γ的增量增加与CD4细胞的增量增加相关（r = 0.711，P < 0.01），但与CD8细胞的增量增加无关。格雷夫斯病患者PBMC对IL-2产生的IFN-γ与甲状腺功能呈负相关，似乎反映了甲状腺功能亢进在这一过程中的影响。这些现象的确切解释仍不清楚。格雷夫斯病、桥本甲状腺炎和类风湿关节炎患者的PBMC对IL-2刺激的IFN-γ反应降低似乎是器官特异性自身免疫病和系统性自身免疫病中出现的一种非特异性现象。这可能是由于自身免疫病中CD4细胞对IL-2反应的下调、IL-2细胞受体水平降低或受体亲和力下降、可溶性IL-2受体增加，或者在所研究的条件下CD4细胞内IL-2信号产生或释放IFN-γ存在缺陷。
