THYROID-CELL SURVIVAL IN COCULTURE WITH AUTOLOGOUS PERIPHERAL OR INTRATHYROIDAL LYMPHOCYTES

OBJECTIVE We have studied lymphocyte induced cytotoxicity and the prod uction of interferon gamma (IFN-gamma) and tumour necrosis factor alph a (TNF-alpha) during coculture of thyrocytes and autologous lymphocyte s from patients with Graves' disease and from normal subjects. PATIENT S Thyroid tissues and lymphocytes were obtained from 28 patients with Graves' disease and from 9 control subjects. MEASUREMENTS Lymphocyte i nduced cytotoxicity was evaluated on autologous thyrocytes using 5 met abolic tests: the MTT assay, the neutral red uptake, lactate dehydroge nase measurement and glutathione assay. IFN-gamma and TNF-alpha measur ements were performed after 1, 5 or 7 days' coculture. RESULTS The lym phocytes isolated from peripheral blood (PB lymphocytes) altered the m orphology and the metabolism of autologous thyrocytes. The intrathyroi dal lymphocytes isolated after Dispase digestion were not toxic wherea s mechanically isolated lymphocytes exerted a little toxicity. No diff erence was seen between Graves' disease and normal cells. The supernat ants from cocultures had higher IFN-gamma levels than those from lymph ocyte cultures. In coculture, PB lymphocytes secreted more IFN-gamma a nd TNF-alpha than intrathyroidal lymphocytes. The PB lymphocyte induce d cytotoxicity was not due to IFN-gamma and TNF-alpha alone. CONCLUSIO N Peripheral blood lymphocytes are cytotoxic in vitro to autologous th yrocytes whereas intrathyroidal lymphocytes exert little or no cytotox icity according to their isolation method. The mechanisms of lymphocyt e induced toxicity remain to be explained.