Action of Globulin and Lymphocytes from Peripheral Blood of Patients with Graves' Disease on Isolated Bovine Thyroid Cells1

Abstract

By modifications of previously described procedures, bovine thyroid cells in suspension were incubated for 4 1/2 hr and cell function was then measured at that time by determining the cell to medium (C/M) ratio of ¹²⁵I-iodide. Thyroid stimulating hormone (TSH) produced a good dose-response curve in this system. Globulin from the serum of a patient with a high titer of long-acting thyroid stimulator (LATS) by bioassay also stimulated the cells to a degree equal to the maximal TSH response. Normal human globulin produced no stimulation. Depression of C/M ratios resulted from doses of both normal and LATS positive globulins above 0.25 mg/ml. This system, however, did not prove to be any more successful in detecting LATS in the globulin fraction of sera from patients with Graves' disease than was the McKenzie mouse bioassay. While papain digestion of the globulin produced even higher C/M ratios in some instances, in other cases papain digestion resulted in less positive C/M ratios. Blood lymphocytes from patients with Graves' disease and normal persons were incubated with bovine thyroid cells. Lymphocytes from Graves' disease patients appeared to cause a slight stimulation of thyroid cell activity (whether from LATS-positive or LATS-negative patients), and this slight stimulation could be abolished by anti-human IgG. This suggested that lymphocytes can stimulate thyroid cells directly, possibly through membrane- bound LATS. Attempts to stimulate the lymphocytes to produce and secrete LATS using phytohemagglutinin (PHA) seemed unsuccessful, since there was an inconsistent response to such stimulated lymphocytes in the thyroid cell suspension system.