Fas ligand expression in thyroid follicular cells from patients with thionamide-treated Graves' disease

Thionamides are used in the treatment of Graves' disease (GD) and act mainl y by inhibiting the organification of iodide, but also lower We levels of t hyroid autoantibodies, sometimes leading to long-term remission. Fas ligand (FasL) induces apoptosis of susceptible cells by cross-linking its own rec eptor, Fas. While Fas is present in a wide variety of normal tissues, Fast expression is limited mainly to cells of the immune system, where it acts a s an effector molecule of cell-mediated cytotoxicity, and to the placenta, brain, eye, and testis where it presumably contributes to their immune-priv ileged status by eliminating infiltrating lymphocytes. We examined immunohi stochemically the presence of Fast in thyroid tissue from 15 glands of thio namide-treated GD patients and in 8 normal thyroid control specimens. We al so investigated We presence of Fast in thionamide-treated thyrocytes in vit ro and their ability to induce Fas-mediated apoptosis in lymphocytes. We fo und that Fast expression was very weak to undetectable in normal thyroid ti ssue and cultured thyrocytes, whereas it was strong in thionamide-treated G D glands and cultured thyrocytes. Methimazole-treated thyrocytes induced Fa st-dependent apoptosis in cocultured lymphocytes, whereas methimazole treat ment of lymphocytes grown in the absence of thyrocytes had no such effect. We conclude that Fast is highly expressed in follicular cells of thyroid gl ands obtained from thionamide-treated Graves' patients and may contribute t o the immunomodulatory effect of thionamides in this disease.