桥本甲状腺炎中细胞凋亡与增殖关系的实验研究

目的探讨桥本甲状腺炎(HT)中Fas、FasL与增殖细胞核抗原(PCNA)的关系.方法以非毒性甲状腺肿(NTG)的标本为对照,采用TUNEL及免疫组织化学双标记法,分别检测16例HT患者甲状腺标本中细胞凋亡水平及PCNA、Fas、FasL的表达及分布.结果凋亡率(AR)在NTG组为(0.9±0.64)%,HT组为(33.92±14.69)%;增殖率(PR)分别为(4.23±2.36)%和(8.45±3.61)%.AR、PR在HT组均显著高于NTG组(P＜0.01).HT中部分甲状腺滤泡细胞PCNA与Fas、FasL共表达;浸润淋巴细胞PCNA高表达,Fas/FasL弱或无表达.结论HT中甲状腺滤泡细胞凋亡与增殖活动均活跃,凋亡水平增高更为显著;浸润淋巴细胞增殖活跃,凋亡少见.其凋亡和增殖的失平衡可能是HT病理改变的主要机制之一.     

AITD甲状腺细胞Fas、FasL的单抗免疫组化测定

测定凋亡相关蛋白Fas、FasL在自身免疫性甲状腺疾病(AITD)病人甲状腺细胞中的表达,以研究细胞凋亡在AITD发病中的作用.本研究采用甲状腺粗针穿刺取甲状腺组织,然后用单克隆抗体免疫组织化学法和图像分析检测甲状腺细胞中Fas、FasL的表达,于电镜下观察结果.Graves病(GD)组Fas、FasL染色强度显著低于对照组(P＜0.01).桥本氏甲状腺炎(HT)组两者染色强度显著高于对照组(P＜0.01).这说明Fas、FasL这两种凋亡相关蛋白在HT病人甲状腺细胞中表达显著增强,而在GD病人中表达较少,进一步证实了细胞凋亡在AITD发病机制中具有重要作用.     

Graves病和桥本甲状腺炎甲状腺组织中凋亡调节蛋白的表达

越来越多的研究表明细胞凋亡参与自身免疫性疾病的发病过程[1,2 ] 。自身免疫性甲状腺疾病的Graves病 (Graves′disease ,GD)和桥本甲状腺炎 (Hashimoto′sthyroiditis ,HT)甲状腺均发生肿大 ,而病理形态、功能及疾病的临床表现迥异 ,其机制尚不清楚。我们对GD及HT甲状腺组织中凋亡调节蛋白Fas、FasL、bcl 2和bax表达进行了对照研究 ,以探讨其与自身免疫性甲状腺疾病发病机制的关系。一、材料与方法1.材料 :5 4例 (男 7例 ,女 4 7例 ,年龄 17～ 6 5岁 )GD及4 1例 (男 12例 ,女 2 9例 ,年龄 2 4～ 6 3岁 )HT患者甲状腺标本来源于我院…     

自身免疫性甲状腺疾病与细胞凋亡

自身免疫性甲状腺疾病(AITD)细胞凋亡存在异常,桥本氏甲状腺炎时,甲状腺细胞Fas表达增强,诱导细胞凋亡,造成甲状腺组织的损伤.Graves病时因Fas表达减弱,bcl-2表达增强而减少了凋亡的发生,从而造成甲状腺滤泡上皮细胞增生肥大.一些物质可以上调或下调甲状腺细胞Fas表达,为AITD的治疗开拓一条新的途径.     

Th17细胞及相关细胞因子在自身免疫性甲状腺疾病中的变化及意义

目的探究Th17细胞及相关细胞因子IL-17、IL-6在自身免疫性甲状腺疾病中的变化及意义。方法收集49例初发自身免疫性甲状腺疾病患者,根据病情分为Graves病初发组和桥本甲状腺炎初发组,随访至治疗后甲状腺功能正常,另设健康对照组。采用流式细胞仪检测外周血中Th17细胞比例,用双抗体夹心酶联法检测血浆IL-17、IL-6水平。结果 IL-17和IL-6在Graves病初发组、桥本甲状腺炎初发组中均明显升高。IL-6在Graves病缓解组中明显下降。IL-17在Graves病缓解组中,桥本甲状腺炎缓解组并无明显下降。Th17细胞在Graves病初发组、桥本甲状腺炎初发组中明显升高。Th17细胞比例与IL-17水平呈正相关,与IL-6无相关性。在桥本甲状腺炎中,Th17和IL-17水平与自身抗体TPO-Ab、TG-Ab呈正相关,在Graves病中,Th17和IL-17水平与特异性抗体TRAB无相关性。结论 Th17细胞可能参与了自身免疫性甲状腺疾病的发病,且与桥本甲状腺炎关系更为密切。     

T细胞受体Vβ基因在自身免疫性甲状腺病病变组织中的表达及意义

目的研究国人Graves病、桥本甲状腺炎甲状腺内浸润T淋巴细胞的T细胞受体(TCR)Vβ基因家族的利用,发现优势利用基因,为阐明自身免疫性甲状腺病(AITD)的T细胞克隆的分布模式及防治提供依据.方法穿刺或手术取得12例Graves病、15例桥本甲状腺炎病人的甲状腺组织,提取RNA.抽取5例Graves病、5例桥本甲状腺炎和7例正常人之外周静脉血,分离外周血淋巴细胞(PBL),提取RNA.以24个Vβ基因家族特异的寡核苷酸为上游引物,以一个Cβ特异的寡核苷酸为下游引物,进行逆转录-聚合酶链反应,比较各个Vβ基因家族的表达.结果Graves病及桥本甲状腺炎患者甲状腺内TCRVβ基因家族的平均表达阳性数分别为(5.3±1.2)个,(13.4±3.0)个;而且Vβ3、Vβ5和Vβ8的表达在Graves病更常见.以上两组病人及正常对照PBL之TCRVβ基因家族的平均表达分别为(23.0±1.0)个,(22.2±1.3)个和(22.4±1.7)个.结论Graves病甲状腺内淋巴细胞的TCRVβ基因显示明显的限制性利用,某些Vβ家族的使用率更高,提示寡克隆扩增的甲状腺抗原特异性T细胞可能与Graves病的发病有关,这可能有重要的治疗意义.相反,桥本甲状腺炎病变内TCRVβ利用的限制性较差或无限制性,可能与随疾病进展,非特异性免疫机制的介入有关.     

Graves病和桥本病甲状腺细胞凋亡与Fas表达的研究

为了研究正常、Graves病 (GD )和桥本甲状腺炎 (HT )甲状腺细胞凋亡和凋亡相关蛋白Fas的变化特征及其临床意义 ,采用细胞培养方法和流式细胞术检测正常、GD和HT甲状腺细胞凋亡率和Fas表达量。结果发现 :(1)GD和HT甲状腺细胞凋亡率明显高于正常甲状腺细胞 (P <0 0 1)。其中 ,尤以HT甲状腺细胞凋亡增加最为显著 ;(2 )HT甲状腺细胞Fas表达阳性率明显高于正常和GD甲状腺细胞 (P <0 0 1) ,而GD与正常对照相比无统计学差异。以上结果表明 ,自身免疫性甲状腺疾病 (AITD )患者甲状腺细胞存在细胞凋亡和Fas表达的异常变化 ,尤以HT为显著 ,提示Fas介导的细胞凋亡参与AITD的发病过程 ,可能与HT甲状腺细胞破坏有关。     

Fas/FasL和Bcl-2在人乳腺癌组织中的表达及其与浸润淋巴细胞的关系

目的通过观察乳腺癌组织中凋亡调节蛋白Fas、FasL、Bcl-2的表达及其与肿瘤浸润淋巴细胞(TIL)的关系,探讨Fas、FasL、Bcl-2与乳腺癌发生、发展的关系,为乳腺癌的生物治疗提供实验依据。方法收集手术切除的人乳腺癌组织和癌旁相对正常乳腺组织。用免疫组织化学方法和图像分析技术对21例乳腺癌标本进行检测。结果乳腺癌组织中Fas的阳性表达率明显低于相对正常乳腺组织(P<0.05),且淋巴细胞浸润性乳腺癌组织中Fas的阳性表达明显低于非浸润性乳腺癌组织(P<0.05);乳腺癌组织中FasL、Bcl-2的阳性表达率明显高于相对正常乳腺组织(P<0.05),且淋巴细胞浸润性乳腺癌组织明显高于非淋巴细胞浸润性乳腺癌组织(P<0.05);乳腺癌组织中Fas阳性淋巴细胞的数量与相对正常乳腺组织相比明显增多(P<0.05);乳腺癌组织Bcl-2阳性淋巴细胞的数量与相对正常乳腺组织相比明显减少(P<0.05)。结论①乳腺癌组织中Fas表达下调和FasL的过度表达,逃避了免疫监视,诱导Fas敏感的TIL凋亡,从而导致肿瘤的生长;②乳腺癌组织中癌基因Bcl-2过度表达及Bcl-2阳性淋巴细胞的低表达,使肿瘤抗凋亡机制过度激活,肿瘤细胞对Fas/FasL易感性较淋巴细胞相对低,导致TIL死亡,而不是肿瘤细胞死亡。     

细胞因子对Graves病甲状腺细胞凋亡及相关蛋白表达的影响

目的：探讨细胞因子（TNF-α、IL-1）诱导Graves病甲状腺细胞凋亡及细胞凋亡相关蛋白表达并与Graves病（GD）发病机制的关系。方法：免疫组化检测50例Graves病甲状腺组织的Fas表达。甲状腺组织取自GD手术标本，采用原代细胞培养方法。采用ELISA法检测细胞培养液中sFas含量。采用RT-PCR方法检测Fas／sFas mRNA。细胞因子诱导Graves病甲状腺细胞凋亡为观察组，设正常人为对照组。结果：观察组和对照组比较细胞凋亡率，有显著性的差异（P〈0．01）。观察组甲状腺细胞sFas、Fas／sFas mRNA含量与对照组比较明显增高（P〈0．01）。结论：细胞因子诱导Graves病甲状腺细胞凋亡及凋亡相关蛋白sFas、Fas／sFas mRNA有一定水平的表达，这些改变可能是细胞因子破坏甲状腺细胞的重要机制之一。     

TGA、TPO-Ab、TRAb和TSH在自身免疫性甲状腺病中的临床应用

目的：探讨TGA、TPO-Ab、TRAb和TSH在自身免疫性甲状腺病中的诊断和鉴别诊断价值。方法：采用化学发光法检测80例自身免疫性甲状腺病患者（桥本甲状腺炎40例,Graves病40例）、50例甲状腺结节患者和40例正常对照者血清TGA、TPO-Ab、TRAb和TSH水平,通过ROC曲线评估最佳诊断阈值。结果：自身免疫性甲状腺病（桥本甲状腺炎和Graves病）患者与非自身免疫性甲状腺疾病（甲状腺结节）患者血清TGA、TPO-Ab的差异有统计学差异（P〈0.01）,非自身免疫性甲状腺病患者组与正常对照组比较无统计学意义（P〉0.05）。在自身免疫性甲状腺病患者中,Graves病患者TRAb水平高于桥本甲状腺炎患者（P〈0.01）,而TSH水平低于桥本甲状腺炎患者（P〈0.01）。通过ROC曲线分析,当TGA、TPO-Ab分别为70.2U/ml、105.65IU/ml时,对自身免疫性甲状腺病的诊断具有最高的灵敏度和特异性;当TRAb、TSH分别为2.25IU/ml、0.60μlU/ml时,对Graves病和桥本甲状腺炎的鉴别诊断价值最高。实验室建立的参考值与试剂盒提供的参考值比较,具有更高的特异性。结论：TGA和TPO-Ab对自身免疫性甲状腺病的诊断具有重要意义,而TRAb和TSH对鉴别诊断Graves病和桥本甲状腺炎具有重要的临床应用价值。每个实验室有必要建立自己的参考范围,为临床和病人提供更准确、有效的信息。     

Analysis of the expression of Fas, FasL and Bcl-2 in the pathogenesis of autoimmune thyroid disorders

To investigate the expression of apoptosis-related protein (Fas, FasL, and Bcl-2) in the pathogenesis of autoimmune thyroid disorders (ATDs), immunohistochemical staining was performed on 20 Hashimoto‘s thyroiditis (HT), 20 Graves‘ disease (GD), and 20 thyroid follicular adenoma (TFA, as control). All the cases expressed Fas, mainly on the cell surface and cytoplasm. FasL was found in 17 cases of the TFA. Bcl-2 was detected in 15 cases of HT, 19 of GD and 17 of TFA. In T FA, a moderate Fas expression and a minimal or no FasL expression was detected on follicular cells. In HT, the follicles adjacent to infiltrating lymphocytes showed increased levels of Fas and FasL expression. A weaker staining of Fas and FasL was exhibited on infiltrating lymphocytes than on thyrocytes. In a comparison of GD with HT, thyrocytes and lymphocytes showed similar Fas staining, but for FasL the staining was rather weaker in HT. The expression of Bcl-2 was nearly identical in GD and TFA, but much weaker on the follicular cells in vicinity of lymphocytes and on the lymphocytes located in germinal centers of HT tissues. The expression of Fas, FasL, Bcl-2 in Hashimoto‘s thyroiditis and Graves‘ disease were almost same. FasL strong expression and Bcl-2 weak expression on the follicles in HT may induce apoptosis. These results provided evidence for expression of Fas, FasL and Bcl-2 in the pathogenesis of autoimmune thyroid disease. The lymphocytes seem not to be directly engaged in the process v/a their own FasL, but they may provide some cytokines that, in turn, upregulate Fas and/or FasL expression to induce apoptosis.     

Identification of apoptotic proteins in thyroid gland from patients with Graves' disease and Hashimoto's thyroiditis

Apoptosis, i.e. natural programmed cell death, is a physiological phenomenon indispensable for normal functioning of the organism. The signal to apoptosis can be started practically in any cell. Disturbances in the apoptosis regulation determine the essential link of the pathogenesis of many diseases, including autoimmune thyroid disorders. The aim of the study was to assess the expression of Fas/FasL and caspase eight in the tissues of the thyroid gland in patients with Graves' disease (GD), non-toxic nodular goiter (NTNG) and Hashimoto's thyroiditis (HT). The analysis of Fas/FasL expression was performed by western blot and immunohistochemical investigation with DAB-visualization and Mayer's hematoxylin staining. Caspase-8 expression in thyroid follicular cells was assayed by western blot method. Identification of the proapoptotic proteins FasL and Fas exhibited their pronounced expression in the thyroid tissue in GD patients (++; ++) and HT (+++; +++) as compared to the NTNG group (0/+; 0/+). Among the study groups, the expression of caspase-8 was revealed in band 55 kDa from patients with autoimmune thyroid diseases. In GD patients, the percentage of thyrocytes with FasL expression correlated positively with TRAb (R = 0.58, p < 0.02). However, no such correlations were noted in HT or non-toxic multinodular goiter. There were no significant correlations between thyroid hormones and the percentage of thyrocytes with Fas and FasL expression. In conclusion, our findings suggest that the changes in the expression of apoptotic molecules on the surface of T lymphocytes and thyroid follicular cells in patients with autoimmune thyroid disorders reflect their substantial involvement in the pathogenesis of GD and HT. In addition, analysis of Fas/FasL and caspase-8 expression in thyroid tissue may indicate the disease activity and immunological phenotype.     

Identification of apoptotic proteins in thyroid gland from patients with Graves' disease and Hashimoto's thyroiditis

Apoptosis, i.e. natural programmed cell death, is a physiological phenomenon indispensable for normal functioning of the organism. The signal to apoptosis can be started practically in any cell. Disturbances in the apoptosis regulation determine the essential link of the pathogenesis of many diseases, including autoimmune thyroid disorders.

The aim of the study was to assess the expression of Fas/FasL and caspase eight in the tissues of the thyroid gland in patients with Graves' disease (GD), non-toxic nodular goiter (NTNG) and Hashimoto's thyroiditis (HT). The analysis of Fas/FasL expression was performed by western blot and immunohistochemical investigation with DAB-visualization and Mayer's hematoxylin staining. Caspase-8 expression in thyroid follicular cells was assayed by western blot method.

Identification of the proapoptotic proteins FasL and Fas exhibited their pronounced expression in the thyroid tissue in GD patients (++; ++) and HT (+++; +++) as compared to the NTNG group (0/+; 0/+). Among the study groups, the expression of caspase-8 was revealed in band 55 kDa from patients with autoimmune thyroid diseases.

In GD patients, the percentage of thyrocytes with FasL expression correlated positively with TRAb (R = 0.58, p < 0.02). However, no such correlations were noted in HT or non-toxic multinodular goiter. There were no significant correlations between thyroid hormones and the percentage of thyrocytes with Fas and FasL expression.

In conclusion, our findings suggest that the changes in the expression of apoptotic molecules on the surface of T lymphocytes and thyroid follicular cells in patients with autoimmune thyroid disorders reflect their substantial involvement in the pathogenesis of GD and HT. In addition, analysis of Fas/FasL and caspase-8 expression in thyroid tissue may indicate the disease activity and immunological phenotype.     

Expression of CD40 and apoptosis related molecules in autoimmune thyroid diseases.

Apoptosis is responsible for the loss of thyrocytes in autoimmune thyroiditis. Recent investigations into the pathogenesis of apoptosis have revealed that the important roles of suicide molecules expression on both thyrocytes and cytotoxic T-lymphocytes. To study the mechanism of thyrocyte loss in various forms of thyroiditis, we evaluated in situ expression patterns of CD40, Fas, and Fas-L on thyrocytes and infiltrating inflammatory cells by immunohistochemical staining of thyroid samples obtained from 49 patients (Graves' disease, n=10: Hashimoto's thyroiditis, n=14; nonspecific lymphocytic thyroiditis, n=11; subacute granulomatous thyroiditis, n=11; normal, n=3). The role of cytotoxic T-lymphocytes was also evaluated by analyzing the expression of granzyme B along with their phenotypic characteristics. CD40 was not expressed on thyrocytes of normal controls while they showed a diffuse expression of Fas and a scattered focal expression of Fas-L. The plump thyrocytes proximal to the inflammatory infiltrates showed more intense expressions of these three molecules in various forms of thyroiditis and a close correlation was found between CD40 and Fas-L expression on thyrocytes. Unlike Fas, which was expressed on infiltrating lymphocytes in all groups, Fas-L was not expressed on infiltrating lymphocytes, except those in subacute granulomatous thyroiditis. Granzyme B expressing activated cytotoxic T-lymphocytes occupied a negligible proportion of CD8+ T-lymphocytes in various forms of thyroiditis, and no difference was found in terms of their proportions according to the type of thyroiditis. These results show the acquisition of CD40, Fas and Fas-L molecules on thyrocytes proximal to inflammatory cell aggregates and the negligible expression of granzyme B and Fas-L on the infiltrating lymphocytes, and suggest that Fas and Fas-L mediated apoptosis of thyrocytes (fratricide) may be more important than T cell-mediated cytotoxicity in various forms of thyroiditis.     

Fas-FasL in Hashimoto's Thyroiditis

Hashimoto's thyroiditis is a common chronic autoimmune disease characterized by the loss of thyroid follicular cells (thyrocytes) that are gradually replaced by lymphocytic infiltration and diffuse fibrosis. These morphological findings suggested that autoreactive T-cell clones were responsible for thyrocyte destruction and hypothyroidism through effector–target cytotoxic recognition. Later, autonomous interaction between thyrocyte Fas and FasL has been proposed as a major mechanism of thyrocyte depletion in Hashimoto's thyroiditis. Here, we analyze the possible role of Fas and FasL in the pathogenesis of Hashimoto's thyroiditis. We suggest that the Fas–FasL system dictates the outcome of the autoimmune response by acting on both immune and target cells.     

Fas ligand gene polymorphisms are not associated with Hashimoto's thyroiditis and Graves' disease

Hashimoto's thyroiditis and Graves' disease represent the two most common autoimmune thyroid disorders. Whereas in Hashimoto's thyroiditis FasL expression causes thyrocytes to undergo apoptosis, additional anti-apoptotic molecules appear to protect these cells in Graves' disease. Mutations of the FasL gene were observed in systemic lupus erythematosus. Given its functional relevance for the pathogenesis of thyroid autoimmunity we wondered whether variants of the FasL gene play a role in Hashimoto's thyroiditis and Graves' disease. We genotyped families with at least one offspring affected by Hashimoto's thyroiditis (n = 86) and Graves' disease (n = 90) for two FasL gene polymorphisms (C -843 T in the promoter, A IVS2nt-124 G in intron 2). Extended transmission disequilibrium (ETDT) and chi(2) testing were performed. Neither polymorphism alone nor the promoter/intron 2 haplotypes (p = 0.91) were associated with Hashimoto's thyroiditis. No association with Graves' disease was observed for the promoter polymorphism (p = 0.91) and the intron 2 "A" allele (57.1%; p = 0.36) or the promoter/intron 2 haplotypes (p = 0.31). Moreover, intron 2 genotyping revealed no difference between an additional 251 patients with Graves' disease and 197 healthy controls (p = 0.37). Italian and German families did not differ for the studied polymorphisms. In conclusion, our data do not suggest common genetic FasL variants to significantly contribute to the pathogenesis of either Hashimoto's thyroiditis or Graves' disease.     

Control of target cell survival in thyroid autoimmunity by T helper cytokines via regulation of apoptotic proteins

After autoimmune inflammation, interactions between CD95 and its ligand (CD95L) mediate thyrocyte destruction in Hashimoto's thyroiditis (HT). Conversely, thyroid autoimmune processes that lead to Graves' disease (GD) result in autoantibody-mediated thyrotropin receptor stimulation without thyrocyte depletion. We found that GD thyrocytes expressed CD95 and CD95L in a similar manner to HT thyrocytes, but did not undergo CD95-induced apoptosis either in vivo or in vitro. This pattern was due to the differential production of TH1 and TH2 cytokines. Interferon gamma promoted caspase up-regulation and CD95-induced apoptosis in HT thyrocytes, whereas interleukin 4 and interleukin 10 protected GD thyrocytes by potent up-regulation of cFLIP and Bcl-xL, which prevented CD95-induced apoptosis in sensitized thyrocytes. Thus, modulation of apoptosis-related proteins by TH1 and TH2 cytokines controls thyrocyte survival in thyroid autoimmunity.     

Intrathyroidal HLA-DR expression and T lymphocyte phenotypes in Graves'' thyrotoxicosis, Hashimoto''s thyroiditis and nodular colloid goitre.

Thyroid surgical biopsies from 21 individuals were examined by a double immunoenzymatic technique with respect to HLA-DR expression and lymphocytic infiltration. HLA-DR positive thyrocytes were observed in two examined Hashimoto goitres and in nine of 11 specimens from patients with Graves' disease. HLA-DR positive thyrocytes were localized to areas harbouring infiltrating lymphocytes, whereas regions with no lymphocytes only rarely expressed HLA-DR antigens. In two specimens of nodular goitre HLA-DR positive thyrocytes were observed in the vicinity of lymphocytic infiltration. Tissues from another three nodular goitres, from one follicular adenoma and from two normal individuals contained no HLA-DR positive thyrocytes and no or only a few lymphocytes. The lymphocytic infiltrates were dominated by cells with the Leu 3a helper/inducer phenotype irrespective of underlying disease, although most pronounced in Hashimoto's thyroiditis. The results indicate that HLA-DR antigens is expressed on thyrocytes in thyroid disorder. The extent of expression correlated with lymphocytic infiltration, which suggests that the two findings are related and of importance for the development of thyroid autoimmunity.     

Modulation of Fas-mediated apoptosis of human thyroid epithelial cells by IgG from patients with Graves' disease (GD) and idiopathic myxoedema

The expression of two autoimmune thyroid diseases, GD and idiopathic myxoedema, is associated with antibodies to the thyroid-stimulating hormone (TSH) receptor. Thyroid stimulating antibodies (TSAb) in GD are TSH agonists and cause hyperthyroidism as well as goitre, whereas thyroid stimulation blocking antibodies (TSBAb) in idiopathic myxoedema are TSH antagonists and cause hypothyroidism and thyroid atrophy. We investigated the effect of antibodies to TSH receptor on Fas-mediated apoptosis of thyroid epithelial cells (thyrocytes). Human IgG was isolated from healthy donors, patients with GD and idiopathic myxoedema. Human thyrocytes were obtained from surgical specimens. Thyrocytes were cultured in the presence or absence of human IgG with or without interferon-gamma (IFN-γ) or IL-1β for a specified time. After incubation, we examined the level of cAMP in cultured supernatants and both Fas and Bcl-2 expression on thyrocytes. In addition, we examined anti-Fas-mediated apoptosis of thyrocytes. Fas expression on thyrocytes was significantly down-regulated by Graves' IgG and TSH, although idiopathic myxoedema IgG did not affect Fas expression on thyrocytes. Idiopathic myxoedema IgG abrogated the effect of TSH on both cAMP production and inhibition of Fas expression on thyrocytes. Treatment of thyrocytes with IL-1β or IFN-γ caused a marked augmentation of Fas expression on thyrocytes. The increase of Fas expression of thyrocytes induced by IL-1β or IFN-γ was significantly suppressed in the presence of TSH or Graves' IgG. Anti-Fas-induced apoptosis of thyrocytes was observed in thyrocytes treated with IL-1β or IFN-γ, but was markedly inhibited in the presence of TSH or Graves' IgG. Furthermore, idiopathic myxoedema IgG abrogated most of the inhibitory effect of TSH on Fas-mediated apoptosis of thyrocytes treated with IL-1β or IFN-γ. Bcl-2 expression of thyrocytes did not change after stimulation with TSH, Graves' IgG, idiopathic myxoedema IgG, IL-1β or IFN-γ. These results suggest that TSAb found in Graves' patients may be potentially involved in the development of goitre by inhibition of Fas-mediated apoptosis of thyrocytes. In addition, TSBAb inhibit the action of TSH and increase the sensitivity toward Fas-mediated apoptosis of thyrocytes, inducing thyroid atrophy seen in patients with idiopathic myxoedema.