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The production of thyroid-stimulating immunoglobulin (TSI) by lymphocytes from patients with Graves’ disease cultured with human thyroid subcellular fractions

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Abstract

The interaction of thyroid-stimulating γ-globulin (LATS) with thyroid fractions has been previously investigated by means of LATS-neutralizing or-absorbing properties. The ability of purified normal human thyroid subcellular fractions to stimulate the production of TSI by lymphocytes from patients with active hyperthyroid Graves’ disease was studied. The activation of adenylate cyclase in human thyroid slices by lymphocyte culture supematants was an index of the production of TSI in the lymphocyte cultures. Four thyroid fractions were employed: the “800 g pellet”, the “50,000 g pellet”, the “105,000 g pellet” and the “thyroglobulin” fraction. Among those various fractions, the “50,000 g pellet” fraction was the most effective and potent stimulant of TSI production by the Graves’ lymphocytes. TSI production in this group was significantly higher than in cultures of Graves’ lymphocytes without antigen added (p<0.01). The “105,000 g pellet” and the “thyroglobulin” fractions were less effective, while the “800 g pellet” fraction was almost ineffective. Lymphocytes from healthy subjects, cultured with the “50,000 g pellet” fraction, showed no significant production of TSI. Moreover, TSH-displacement study and electron microscopic findings demonstrated that this “50,000 g pellet” fraction contains abundant membrane components of the thyroid gland. These results suggest that the normal human thyroid plasma membrane component(s) may be the most important subcellular fraction(s) acting as an antigenic stimulant of lymphocytes from patients with Graves’ disease (causing them to produce thyroid-stimulating immunoglobulin). Furthermore, there seems to be no need for an antigenic change in this system.

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Research Fellows of the Wellesley Hospital Research Foundation

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Sugenoya, A., Trokoudes, K., Row, V.V. et al. The production of thyroid-stimulating immunoglobulin (TSI) by lymphocytes from patients with Graves’ disease cultured with human thyroid subcellular fractions. J Endocrinol Invest 1, 245–251 (1978). https://doi.org/10.1007/BF03350388

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