Expression of CD40 and apoptosis, related molecules in autoimmune thyroid diseases
Expression of CD40 and apoptosis, related molecules in autoimmune thyroid diseases
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DOI：
10.3349/ymj.2001.42.5.488
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发表时间：
2001-10-01
影响因子：
2.4
通讯作者：
Yang, WI
中科院分区：
文献类型：
--
作者：
Kie, JH;Cho, MS;Yang, WI
细胞凋亡是自身免疫性甲状腺炎中甲状腺细胞损失的主要原因。近年来对细胞凋亡发病机制的研究表明，自杀分子的表达在甲状腺细胞和细胞毒性t淋巴细胞中都起着重要作用。为了研究各种形式甲状腺炎中甲状腺细胞损失的机制，我们通过免疫组化染色对49例患者（Graves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）的甲状腺细胞和浸润性炎症细胞的CD40、Fas和Fas- l的原位表达模式进行了评估。通过分析颗粒酶B的表达及其表型特征来评价细胞毒性t淋巴细胞的作用。正常对照甲状腺细胞不表达CD40， Fas呈弥漫性表达，Fas- l呈散在性表达。在各种形式的甲状腺炎中，炎性浸润近端丰满的甲状腺细胞中这三种分子的表达更为强烈，且甲状腺细胞中CD40与Fas-L的表达密切相关。与Fas在所有组浸润淋巴细胞上表达不同，Fas- l在浸润淋巴细胞上不表达，除亚急性肉芽肿性甲状腺炎外。表达活化的细胞毒性t淋巴细胞的颗粒酶B在各种甲状腺炎中占CD8+ t淋巴细胞的比例可以忽略不计，其比例根据甲状腺炎的类型没有差异。这些结果表明，CD40、Fas和Fas- l分子在炎性细胞聚集体附近的甲状腺细胞上获得，而浸润淋巴细胞上颗粒酶B和Fas- l的表达可以忽略，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（杀精）可能比T细胞介导的细胞毒性更重要。
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.