Abstract. To investigate the relationships between lymphocyte subsets and thyroid function, peripheral blood lymphocytes were analysed with cell surface antigens of activated (HLA-DR+) T, helper T (CD4+2H4−, CD4+4B4+) and suppressor-inducer T (CD4+2H4+, CD4+4B4−) cells subsets in 56 patients with Graves' disease, 16 patients with Hashimoto's thyroiditis, 7 patients with typical subacute thyroiditis and 2 patients with the thyrotoxic phase of autoimmune thyroiditis. Both patients with Graves' disease and Hashimoto's thyroiditis had increased percentages of HLA-DR+T (Ia+CD3+) cells as well as HLA-DR+ helper-inducer T (Ia+CD4+) cells, which seemed to be independent of treatments. The percentage of HLA-DR+ suppressor-cytotoxic T (Ia+CD8+) cells was increased in euthyroid or hypothyroid patients with Graves' disease following treatment, but was normal in hyperthyroid patients. The percentages of Ia+CD4+ cells and Ia+CD8+ were also increased in patients with thyrotoxic phases of subacute thyroiditis and autoimmune thyroiditis, whereas these abnormal values normalized in the remission phase. These findings suggest that an increase in Ia+CD4+ cells characteristically occurs during immune system activation in patients with hyperthyroid Graves' disease, Hashimoto's thyroiditis and the thyrotoxic phase of subacute thyroiditis, whereas the activated CD8+ cells in Graves' disease are induced by antithyroidal therapy.

A 38-year-old woman with rheumatoid arthritis who developed Wegener's granulomatosis is described. Wegener's granulomatosis appeared with saddle nose, perforation in her nasal septum, and granuloma in the nasal cavity. Laboratory evaluation showed a positive rheumatoid factor and circulating immune complex. Radiographic examination revealed ankylotic changes in both wrist and elbow joints. Bilateral anosmia and other disease manifestations completely responded to treatment with oral cyclophosphamide and prednisolone.

To determine whether serum immunoglobulin in addition to epidermal growth factor (EGF) augment growth in human thyroid cells, effects of these factors on thyrocytes were tested using IgG derived from 34 patients with Graves' disease and 12 normal subjects. The cell growth was estimated by [3H]-thymidine uptake, cell cycle determined by FACS analysis and the expression of c-fos mRNA in monolayer thyrocytes enzymatically prepared from Graves' thyroid. The addition of IgG taken from patients with Graves' disease inhibited the [3H]-thymidine uptake compared to that taken from control subjects. IgG taken from Graves' disease suppressed EGF-induced increase of S + G2/M phase in cell cycle and the expression of c-fos mRNA, while those taken from normal subjects did not affect at all. [3H]-thymidine uptake was more suppressed by IgG from patients with a smaller-sized goiter than by those with a larger-sized one. There was a negative correlation between the suppression of [3H]-thymidine uptake and levels of TBII (p less than 0.05). There was no correlation between the degree of suppression and the levels of T3, T4, TSAb, TSBAb or MCHA. Thus, in conclusion, IgG derived from sera of Graves' may inhibit the growth of Graves' thyrocytes, leading to the determination of the goiter size.

Abstract. Monensin is a carboxylic ionophore which perturbs the structure and function of the Golgi apparatus and lysosomes. In the present study, we investigated the functional significance of these organella in the growth factor-mediated cell proliferation in cultured human thyroid cells from normal and Graves' disease. DNA synthesis was estimated by [3H]-thymidine uptake and flow cytometric analysis. Monensin inhibited both [3H]-thymidine uptake in a dose-dependent manner and the transition of G1 to S phase determined by flow cytometric analysis. Monensin partially blocked the effect of bovine TSH in normal thyroid cells.[3H]-thymidine uptake was suppressed to 56.7±37.3% of the control value with bTSH and monensin, but it was still higher than those with monensin alone (21.9± 15.0% of the control). The percentage of cells in the S phase was also increased from 7.64±1.919 with monensin alone to 11.54±2.82% with bTSH at t=24h. Forskolin or 12-0-tetradecanoylphorbol 13-acetate (TPA) could not mimic the action of TSH. On the other hand, insulin and EGF most effectively counteracted monensin-induced inhibition of DNA synthesis in Graves' thyroid cells.[3H]-thymidine uptake was not completely inhibited, being 73.5±24.0% with EGF, 105.0±25.4% with insulin, and 49.2±6.6% with monensin alone, respectively. The percentage of cells in the S phase also increased from 8.31±2.61% with monensin alone to 11.25±4.27% with EGF and 12.86±3.12% with insulin. In conclusion, the functional maintenance of the Golgi apparatus and lysosomes is necessary for DNA synthesis in both normal and Graves' thyroid cells, in which bTSH, insulin, and EGF might be differently involved in the regulation of DNA synthesis.

To investigate whether partial inhibition of DNA synthesis affects the growth of thyroid cells, human thyroid cells were cultured in the presence of aphidicolin for 24h. After removal of aphidicolin, the growth of thyroid cells was evaluated by [3H] thymidine uptake and analysis of cell cycle by flow cytometry. In Graves' thyroid cells, [3H] thymidine uptake and the percentage of cells in S+G2/M phase increased during 24 hours after washout of aphidicolin, whereas those were not augmented in normal thyroid cells. Thus, the acceleration of DNA synthesis occurred after the partial inhibition of it by aphidicolin in Graves' thyroid cells, but not in the normal thyroid cells. This phenomenon might, at least in part, explain the difference of growth regulation between Graves' and normal thyroid cells.