Kie J H, Cho M S, Yang W I
Department of Pathology, Yonsei University College of Medicine, C.P.O. Box 8044, Seoul 120-752, Korea.
Yonsei Med J. 2001 Oct;42(5):488-96. doi: 10.3349/ymj.2001.42.5.488.
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.
细胞凋亡是自身免疫性甲状腺炎中甲状腺细胞丢失的原因。最近对细胞凋亡发病机制的研究表明，自杀分子在甲状腺细胞和细胞毒性T淋巴细胞上的表达起着重要作用。为了研究各种形式甲状腺炎中甲状腺细胞丢失的机制，我们通过免疫组织化学染色对49例患者（格雷夫斯病，n = 10；桥本甲状腺炎，n = 14；非特异性淋巴细胞性甲状腺炎，n = 11；亚急性肉芽肿性甲状腺炎，n = 11；正常，n = 3）的甲状腺样本进行检测，评估甲状腺细胞和浸润性炎症细胞上CD40、Fas和Fas-L的原位表达模式。通过分析颗粒酶B的表达及其表型特征，也评估了细胞毒性T淋巴细胞的作用。正常对照组的甲状腺细胞不表达CD40，而Fas呈弥漫性表达，Fas-L呈散在局灶性表达。在各种形式的甲状腺炎中，靠近炎症浸润处的饱满甲状腺细胞这三种分子的表达更强，并且在甲状腺细胞上CD40和Fas-L的表达之间发现密切相关性。与所有组浸润淋巴细胞上均表达的Fas不同，除亚急性肉芽肿性甲状腺炎外，浸润淋巴细胞上不表达Fas-L。在各种形式的甲状腺炎中，表达颗粒酶B的活化细胞毒性T淋巴细胞在CD8 + T淋巴细胞中所占比例可忽略不计，并且根据甲状腺炎类型，它们的比例没有差异。这些结果表明，炎症细胞聚集附近的甲状腺细胞上获得了CD40、Fas和Fas-L分子，并且浸润淋巴细胞上颗粒酶B和Fas-L的表达可忽略不计，这表明在各种形式的甲状腺炎中，Fas和Fas-L介导的甲状腺细胞凋亡（自相残杀）可能比T细胞介导的细胞毒性更重要。
