Graves病甲状腺共刺激分子GL50-ICOS的表达及其免疫病理意义

目的 研究共刺激分子GL50-ICOS在Graves病(GD)甲状腺组织中的表达及其免疫病理意义.方法运用细胞培养、流式细胞术、RT-PCR、Western印迹和免疫组化技术,检测GD甲状腺组织和原代培养的甲状腺滤泡细胞(TFC)共刺激分子GL50和ICOS的表达.结果 (1)与正常同龄对照相比,CD4+CD28-T细胞群体在GD患者外周血中显著升高,其表面ICOS表达上调.(2)RT-PCR显示,GD患者甲状腺组织中有ICOS mRNA表达,与对照非毒性甲状腺肿(NTG)组相比具有统计学差异(P＜0.01).(3)Western印迹显示,GL50蛋白在10例GD患者组织中全部表达,较对照组差异有统计学意义(P＜0.01).(4)与对照甲状腺腺瘤组相比,GL50在20例GD患者组织切片中全部检出,而对照组无阳性表达(P＜0.01).(5)炎性细胞因子刺激体外原代培养的甲状腺滤泡细胞表面上调表达GL50(P＜0.05).结论共刺激分子GL50-ICOS在Graves病甲状腺组织异常表达.

Co-stimulatory signal GL50-ICOS expression in thyroid of Graves' disease and its immune pathogenetic significance

Objective To study the expression of co-stimulatory molecules, GL50-ICOS, in thyroid tissue of patients with Graves' disease (GD) and to explore their relationship with the immune pathogenesis of GD.Methods RT-PCR, Western blot, immunohistochemistry were applied to detect the expression of GL50-ICOS in thyroid of GD. Thyrocytes were cultured in the absence or presence of pro-inflammatory cytokines. The expression of GL50 on thyroid follicular cells (TFC) was further measured by flow cytometry. Results (1) In GD patients,the percentage of CD4+ CD28- T cells was significantly increased as compared with the control healthy individuals. The expression of co-stimulatory molecule ICOS was up-regulated. (2) The mRNA level of ICOS was significantly increased in GD patients than that in nontoxic goiter(NTG) patients(P＜0.01). (3)Compared with NTG control group, the GL50 protein expression was much higher in thyroid tissues of GD patients (P ＜0.01). (4)The results of immunohistochemistry showed that GL50 expression was observed in all GD thyroid tissues, while no expression of GL50 was detected in NTG thyroid tissues(P＜0. 01). (5) The expression of GL50on primary cultured thyroid follicular cells was significantly increased under the stimulatation of pro-inflammatory cytokines in vitro. Conclusion GL50-ICOS is expressed abnormally in thyroid tissue of patients with GD.