自身免疫甲状腺病循环和甲状腺内细胞毒性T细胞（T8／S6F1…

应用新型单克隆抗体Ｔ８／Ｓ６Ｆ１和流体细胞测定仪双色荧光程序检测了１５例Ｇｒａｖｓｅ病和８例Ｈａｓｈｉｍｏｔｏ甲状腺炎患者循环和甲状腺内的细胞毒性Ｔ细胞的分布，传统的单克隆抗体ＣＤ８（ＯＫＴ８或Ｌｅｕ２）仅能检测含有两个次亚群－抑制Ｔ细胞和细胞毒性Ｔ细胞的ＴＳ／ＴＣＴ细胞亚群，不能将它们区别开来。本文应用的单克隆抗体Ｔ８／Ｓ６Ｆ１首次能够单独测定ＴＣ亚群。Ｇｒａｖｅｓ病和Ｈａｓｈｉｍｏｔｏ甲状患者     

自身免疫性甲状腺疾病巨噬细胞浸润与T细胞活化

用单核/巨噬细胞（Mo/Mφ）特异性单克隆抗体Ki-M8和抗T细胞活化抗原TLiSAl、Tac单抗对37例自身免疫性甲状腺疾病（AITD）作免疫细胞化学研究。结果表明:无论是桥本甲状腺炎还是Graves病或甲亢合并甲状腺炎,甲状腺组织中均有一定数目Mφ浸润和活化T细胞聚集;甲状腺单个核细胞中Mφ所占比例与活化抗原阳性细胞所占比例呈正相关。认为在AITD甲状腺中Mφ浸润能促进其邻近部位T细胞活化和增殖。     

自身免疫甲状腺疾病T细胞受体的表现型

应用抗β链可变区(Vβ)的3种单克抗隆体(Vβ_5,Vβ_6,Vβ_(12))和一种抗γ链可变区(Vγ)的单克隆抗体检测Graves病和桥本病患者的外周血液及甲状腺内浸润的T细胞的受体表现型。以正常人的外周血液作为对照,患者的Vβ阳性T细胞分布未见异常。但7例受检者的甲状腺中有5例Vγ阳性的T细胞增加。在未经治疗的Graves病患者的外周血液中Vγ阳性的T细胞未见增加。结果提示:自身免疫甲状腺疾病的T细胞反应可能是多克隆的。表达为Vγ型受体的T细胞可能在桥本甲状腺炎中发挥了一定的作用。     

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(autoimmune thyroid disease．AITD)是人类常见的自身免疫性疾病，主要包括Graves’病(GD)和桥本氏甲状腺炎(Hashimoto’s thyroiditis,HT)。AITD的病变部位主要发生在甲状腺，属于器官特异性自身免疫性疾病。多数学者研究认为，AITD发病是自身抗体的免疫应答或特异性T细胞介导的细胞免疫引起甲状腺组织的免疫损     

慢性乙型肝炎外周血细胞毒性T细胞亚群（Tc1／Tc2）失衡的研究

目的研究细胞毒性T细胞亚群(Tc1/Tc2)在慢性乙型肝炎(CHB)和乙型肝炎肝硬化(LC)发病机制中的作用。方法用流式细胞仪测定Tc细胞亚群特异性的细胞表面双标志物Tc1(CD8/CCR5)、Tc2(CD8/CD30)的方法,测检了75例CHB、40例LC患者和20例正常人(NC)外周血Tc1、Tc2水平。结果CHB和LC患者外周血水平Tc1明显高于NC组(P<0.01);LC组Tc2小于CHB和NC组(P<0.05);重型CHB患者Tc1、Tc2均明显低于其它CHB患者(P<0.01);CHB和LC组Tc1/Tc2明显高于NC组(P<0.01)。结论CHB患者Tc细胞亚群(Tc1/Tc2)与正常人存在着差异,Tc细胞亚群失衡可能在CHB、LC患者病情的进展以及预后中起着重要作用。     

Graves病患者外周血T细胞亚群和NK细胞活性的变化

我们以单克隆抗体技术检测了Graves病(GD)患者治疗前外周血T细胞亚群,以~(51)Cr释放法动态观察了患者在治疗不同时期NK细胞活性的变化,并探讨了GD与NK细胞功能的关系以及抗甲状腺药物对其的影响作用。     

自身免疫性甲状腺疾病中Th1/Th2细胞平衡

辅助性T细胞(Th)可以根据其分泌的细胞因子而分为Th1和Th2两种不同的亚群,Th1/Th2失衡在自身免疫性甲状腺疾病的发病机制中起重要作用.Graves病可能以Th2型细胞因子介导的体液免疫为主,桥本甲状腺炎可能以Th1型细胞因子介导的细胞免疫为主,而Th1/Th2细胞因子共同参与Graves突眼的形成.     

自身免疫性甲状腺疾病中Thl／Th2细胞平衡

辅助性T细胞(Th)可以根据其分泌的细胞因子而分为Thl和Th2两种不同的亚群，Thl／Th2失衡在自身免疫性甲状腺疾病的发病机制中起重要作用。Graves病可能以Th2型细胞因子介导的体液免疫为主，桥本甲状腺炎可能以Thl型细胞因子介导的细胞免疫为主，而Thl／Th2细胞因子共同参与Graves突眼的形成。     

CD4+ CD25+ 调节性T细胞与自身免疫性甲状腺疾病

CD4+ CD25+ 调节性T细胞为新近发现的一群功能成熟的T细胞亚群.其特征性表达叉头盒蛋白3(Foxp3)分子,专职免疫无能和免疫抑制,在维持外周免疫耐受,防止自身免疫性疾病发病中起着极为关键的作用.CD4+ CD25+ 调节性T细胞在自身免疫性甲状腺疾病(AITD)发病中的作用引起了人们的关注.动物实验发现CD4+ CD25+ 调节性T细胞存在与否决定了实验动物是否发生实验性自身免疫性甲状腺炎(EAT)和Graves病.人体研究发现CD4+ CD25+ 调节性T细胞数目和功能异常与人AITD发生密切相关.这些研究结果提示,CD4+ CD25+ 调节性T细胞可能在AITD发病中起重要作用.     

Graves病患者经他巴唑治疗后T细胞亚群的变化

我们过去的研究工作表明Graves病(GD)患者具有外周血T细胞亚群的异常,即辅助性T细胞(T_H)增多;抑制性T细胞(Ts)减少;T_H/T_s比值升高。同时,通过观察他巴唑对自身混合淋巴细胞反应的影响,我们也证明了他巴唑具有免疫调节作用。本文在此基础上,进一步观察了经他巴唑治疗不同时间后GD患者T细胞亚群的变化,以深入探讨本病患者的T细胞亚群与临床治疗的关系。     

自身免疫性甲状腺疾病生长刺激抗体的研究

以鼠甲状腺细胞株（ＦＲＴＬ－５）为靶细胞，３Ｈ－ＴｄＲ掺入为生长指标和ｃＡＭＰ产生量为功能指标，对８６例自身免疫性甲状腺病（ＡＩＴＤ）甲状腺生长刺激抗体（ＴＧＡｂ）及部分患者甲状腺功能刺激抗体（ＴｓＡｂ）活性进行了测定。甲状腺Ⅱ°和Ⅲ°肿大的活动性Ｇｒａｖｅｓ病（ＧＤ）的ＴＧＡｂ阳性率为６４％，而Ⅰ°者为２１％。ＧＤ的ＴＧＡｂ与ＴｓＡｂ括性及Ｔ３值不相关。散发性甲状腺肿大患者ＴＧＡｂ阳性率为３１％（５／１６）。提示ＧＤ申状腺肿大与患者体内存在的能使甲状腺细胞增生的ＴＧＡｂ有关。散发性甲状腺肿大患者体内存在自身免疫性紊乱。     

THYROID STIMULATING ANTIBODIES AND METASTATIC THYROID CARCINOMA

A patient with previously treated follicular carcinoma of the thyroid developed Graves' disease with a high titre of thyroid-stimulating antibodies (TSAb). He developed functioning pulmonary metastases leading to hyperthyroidism. Levels of TSAb paralleled the functional status of the metastases suggesting that hyperfunction of the neoplastic tissues was caused by TSAb.     

THYROID FUNCTION IN EUTHYROID SUBJECTS WITH AUTONOMOUS THYROID NODULES

The biochemical abnormalities in euthyroid subjects with autonomous thyroid nodules have been defined. Seven subjects have been studied in detail. None were hyperthyroid and conventional tests of thyroid function were normal. The characteristic abnormalities were noted on scanning. The absent response to TRH demonstrated that pituitary TSH suppression was present in all subjects. A moderate elevation of serum triiodothyronine (T₃) concentration, 1.89-3.07 ng/ml, was noted. It is concluded that autonomous nodules in the euthyroid subjects studied are associated with elevated T₃ levels sufficient to produce pituitary suppression but not high enough to be associated with the clinical manifestations of hyperthyroidism.     

THE ASSAY FOR THYROID STIMULATING IMMUNOGLOBULINS USING CULTURED HUMAN THYROID CELLS

Recent reports have shown that thyroid-stimulating immunoglobulins (TSI) may be detected by measuring cyclic AMP increases in cultures of isolated thyroid cells in response to added patient immunoglobulins (Ig). We have compared the frequency that TSI may be detected in the Ig fraction of 114 sera from 112 patients with a variety of thyroid disorders, to the presence of thyrotrophin binding inhibitor Ig (TBII). Whereas the sera of 46 out of 48 (95.6%) patients with untreated thyrotoxic Graves' disease had detectable TSI, only 26 out of 48 (54.2%) had detectable TBII. We did not find any significant correlation between TSI and TBII for these patients but there was a significant correlation between TSI and both serum T3 (r = +0.55, P less than 0.01) and T4 (r = +0.50, P less than 0.01). Twelve patients were studied at the time of relapse of thyrotoxicosis due to Graves' disease. All sera contained detectable TSI whereas only one contained detectable TBII. Of the sera from 20 patients in remission after antithyroid drug therapy three were positive for TSI. One of these samples as well as two others had detectable TBII. The two samples with TBII in the absence of TSI came from patients who had developed hypothyroidism. TSI were detected in the serum of one out of nine patients with Hashimoto's thyroiditis but not in the sera of 20 other patients with a variety of non-autoimmune thyroid disorders including five patients with thyrotoxicosis not due to Graves' disease. However TSI was found in the sera of three out of five patients with exophthalmos and no history of hyperthyroidism.(ABSTRACT TRUNCATED AT 250 WORDS)     

EVIDENCE FOR THYROID ANTIGEN-REACTIVE T LYMPHOCYTES INFILTRATING THE THYROID GLAND IN GRAVES''DISEASE

We have investigated the relative distribution and some in vitro functions of thyroid-infiltrating immunocompetent cells obtained at fine-needle aspiration biopsy in twelve patients with Graves' disease and thirteen patients with Hashimoto's thyroiditis. In both disorders the predominant (57--59%) thyroid-infiltrating cell was a small lymphocyte. Significant numbers of plasma cells (10%) were seen only in Hashimoto's thyroiditis. Mononuclear phagocytes (monocytes plus macrophages) were present in similar numbers (12--18%) in both disorders. In both Graves' and Hashimoto's disease there was a relative reduction of (thymus-dependent) lymphocytes in the thyroid gland as compared to the blood. Blood and thyroid-infiltrating T lymphocytes were tested for in vitro cell-mediated immunity (CMI) to thyroid antigen in the leucocyte migration inhibition test (LMT). CMI was readily demonstrated in the blood of most patients with Graves' and Hashimoto's disease. When the thyroid-infiltrating lymphocytes were tested for CMI in the LMT, only the infiltrating cells from patients with Graves' disease displayed CMI, whereas the thyroid-infiltrating lymphocytes in Hashimoto's disease were negative. Fractionation of the immunocompetent cells demonstrated that the thyroid antigen-induced LMT response of blood and thyroid-infiltrating lymphocytes in Graves' disease is a T lymphocyte-dependent phenomenon.     

THYROID FUNCTION IN CHORIOCARCINOMA: DEMONSTRATION OF A THYROID STIMULATING ACTIVITY IN SERUM USING FRTL-5 and HUMAN THYROID CELLS

Hyperthyroidism is a well recognized complication of gestational trophoblastic tumours (GTT) and may be due to high circulating concentrations of human chorionic gonadotrophin (hCG) or its variants. We have studied 24 clinically euthyroid women with GTT. Eight were biochemically hyperthyroid with low or undetectable serum thyrotrophin (TSH) and had a mean serum hCG of 361.2 x 10(3) IU/l compared to 76.2 x 10(3) IU/l in the other patients (P less than 0.01). Purified hCG stimulated iodide uptake into FRTL-5 cells with 25 x 10(3) IU/l being equivalent in potency to 1 mU/l of thyrotrophin (TSH). Sixteen out of the 24 sera (67%) stimulated iodide uptake when applied to the cells at a 1:10 dilution. Sera from all eight hyperthyroid patients contained thyroid stimulating activity. The mean hCG concentration in the 16 stimulatory sera was 238.2 x 10(3) IU/l compared to 37.1 x 10(3) IU/l in the other eight sera (P less than 0.01). Six men with hCG-secreting testicular tumours were biochemically euthyroid although three of their sera stimulated iodide uptake into FRTL-5 cells. In human thyroid cells the mean cAMP production over 4 h with sera from five healthy controls was 54.2 +/- 1.81 pmol/mg cell protein compared to 67.0 +/- 3.8 pmol/mg protein with sera from five choriocarcinoma patients (P less than 0.02). Serum from patients with gestational trophoblastic tumours contains a thyroid stimulating activity which may be hCG and whose presence correlates with hyperthyroidism.     

LONG-ACTING THYROID STIMULATOR AND THYROID FUNCTION IN RELATIVES OF PATIENTS WITH GRAVES''DISEASE

In ten families, fifty relatives and seven husbands of ten patients with untreated Graves’disease were submitted to clinical examination, biological and immunological investigations. They were compared with fifty control subjects. In the relatives, thyroid diseases were found in 26%, positive LATS-IgG responses in 30%, thyroid antibodies in 23% and abnormal NBEI in 30%. The mean LATS response was significantly greater than in controls. With one exception no overt hyperthyroidism was found in the relatives on the basis of serum PBI, T₃ resin uptake test, total T₄ and TSH level. From the analysis of the pedigrees, no definite mode of inheritance can be found for LATS and NBEI. These data suggest the existence of a thyroid metabolic anomaly in the families of patients with thyrotoxicosis and argue against LATS as the cause of the hyperthyroidism of Graves’disease.