Interferon-gamma protects human thyroid epithelial cells against cell-mediated cytotoxicity.

Interferons have been shown to have antagonistic effects on cell-mediated cytotoxicity. In the present study, we investigated various types of immunologically mediated cytotoxic reactions with a 51chromium release assay, using human thyroid cells as targets, which were cultured in the presence and absence of interferon-gamma (IFN-gamma). Antibody-dependent cell-mediated cytotoxicity (ADCC), natural killer (NK) cell-mediated cytotoxicity, and autologous lymphocyte-mediated cytotoxicity (ALC) were measured utilizing thyroid tissue, sera and lymphocytes from patients with autoimmune thyroid disease as well as from normal subjects. ADCC, determined with sera from patients with Hashimoto's thyroiditis, was reduced by 70% when the thyroid target cells were cultured in the presence of 1000 U human IFN-gamma/ml culture medium. Similarly, natural killer cell-mediated cytotoxicity, as well as autologous lymphocyte-mediated cytotoxicity, was significantly reduced after pretreatment of thyroid target cells with 500-1000 U IFN-gamma/ml culture medium. Although it is known that IFN-gamma renders target cells resistant to NK cell-mediated lysis, this is the first report on this effect using human epithelial cells, which may have major implications for the suggested role of IFN-gamma in the induction and perpetuation of autoimmune thyroid disease.