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

Apoptosis is responsible for the loss of thyrocytes in autoimmune thyroidit is. 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 v arious forms of thyroiditis, we evaluated in situ expression patterns of CD 40, Fas, and Fas-L on thyrocytes and infiltrating inflammatory cells by imm unohistochemical staining of thyroid samples obtained from 49 patients (Gra ves' 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 exp ression 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 thy rocytes proximal to the inflammatory infiltrates showed more intense expres sions of these three molecules in various forms of thyroiditis and a close correlation was found between CD40 and Fas-L expression on thyrocytes. Unli ke Fas, which was expressed on infiltrating lymphocytes in all groups, Fas- L was not expressed on infiltrating lymphocytes, except those in subacute g ranulomatous thyroiditis. Granzyme B expressing activated cytotoxic T-lymph ocytes occupied a negligible proportion of CD8+ T-lymphocytes in various fo rms of thyroiditis, and no difference was found in terms of their proportio ns according to the type of thyroiditis. These results show the acquisition of CD40, Fas and Fas-L molecules on thyrocytes proximal to inflammatory ce ll 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 cyto toxicity in various forms of thyroiditis.