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Effects of gamma-interferon and tumor necrosis factor alpha on thyroid cells: induction of class II antigen and inhibition of growth stimulation.

A functioning rat thyroid cell line (FRTL5) was used to study interactions of thyrotropin (TSH) and various cytokines on expression of class I and II major histocompatibility complex (MHC) antigens and on growth stimulation. Only gamma-interferon (gamma-IFN) affected MHC antigen expression, i.e., to enhance class I, that was constitutive, and to induce class II. A concomitant, but probably not directly related, effect of gamma-IFN was to diminish growth stimulation, as effected by TSH and other activators of adenylate cyclase and measured by DNA increase and enhanced incorporation of [3H]thymidine into DNA. Stimulation of growth by tetradecanoylphorbol ester was also decreased by gamma-IFN. These effects of gamma-IFN were mimicked to some degree by tumor necrosis factor but there was major synergism between the two cytokines. Enhanced accumulation of cAMP by TSH and other agents was not diminished in these experiments. Flow cytometry analysis showed that inhibition of growth stimulation involved blocking of the passage of cells from the G0/1 phase to the S phase. The data may have relevance to goiter size in autoimmune thyroid disease.