ACTION OF PERIPHERAL OR INTRATHYROIDAL LYMPHOCYTES ON AUTOLOGOUS THYROCYTES CULTURED IN FOLLICLES IN COLLAGEN GEL

We have studied the action of peripheral blood lymphocytes (PBLs) and intrathyroidal lymphocytes (ITLs) on the biochemical and hormonal meta bolism of autologous thyrocytes cultured in follicles in a collagen ge l. The production of tumour necrosis factor alpha (TNF-alpha) in cultu re was also measured. Thyroid tissues and lymphocytes were obtained fr om ten patients with Graves' disease and from five control subjects. L ymphocyte-induced cytotoxicity was evaluated in autologous thyrocytes cultured in a collagen gel by several tests: neutral red uptake, lacta te dehydrogenase activity and glutathione level. Hormonal metabolism w as assessed by evaluating tri-iodothyronine (T-3) and total cAMP produ ction under TSH stimulation. TNF-alpha levels were measured in superna tants after 5 days of coculture. PBLs altered biochemical metabolism, T-3 synthesis and cAMP production in autologous thyroid follicles. The se inhibitions were greater than those obtained with ITLs. No differen ce was seen between cells obtained from patients with Graves' disease and those from normal subjects. TNF-alpha levels secreted by PBLs were higher than those secreted by ITLs. The concentrations of this cytoki ne decreased in coculture. Significant correlations were observed betw een the decrease in biochemical and hormonal parameters and TNF-alpha levels. Exogenous TNF-alpha and high doses of interferon gamma inhibit ed follicle metabolism, especially hormone secretion. In conclusion, t hyrocytes cultured in follicles provide a more sensitive model than mo nolayer cultures for analysis of lymphocyte-induced interactions. Lymp hocytes gradually inhibit the biochemical and hormonal metabolism of a utologous thyroid follicles depending on the isolation method. These a lterations may be particularly attributed to TNF-alpha secreted by lym phocytes. The cytokine-induced inhibition of thyroid hormonal function apparently involves the adenylate cyclase system.