Effects of γ-interferon and tumor necrosis factor α 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 γ-interferon (γ-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 γ-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 γ-IFN. These effects of γ-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 g 0 1 phase to the S phase. The data may have relevance to goiter size in autoimmune thyroid disease

Production and partial characterization of interleukin 2 induced by periodic acid oxidation of lymphocyte membranes

Murine splenocytes, when stimulated to undergo blastogenesis by H 5IO 6 oxidation, produced a lymphokine with a spectrum of properties identical to that generally ascribed to IL-2 released by lectin-stimulated cells. These included the sustained propagation of IL-2-dependent CT6 cells, as well as identical thermal and enzymatic stabilities. Cell membrane carbonyls generated in situ by the oxidation of cell membranes served as triggers for subsequent IL-2 production by the activated cells. Reduction of membrane carbonyls by NaBH 4, and their addition reaction with NaHSO 3 and NH 2OH abrogated cell activation and inhibited, but did not abolish, IL-2 production. None of the specific carbonyl reagents, e.g., NaBH 4, NaHSO 3, and NH 2OH, have by themselves induced blastogenic transformation, although they did elicit IL-2 production. It is therefore concluded that cell membrane carbonyls serve as triggers for IL-2 production by H 5IO 6-transformed cells, although an increased rate of DNA synthesis per se is not an indispensable precondition for IL-2 synthesis