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.
Similar content being viewed by others
References
Volpé R. The role of autoimmunity in hypoendocrine and hyperen-docrine function. With special emphasis on autoimmune thyroid disease. Ann. Intern. Med. 87: 86, 1977.
Beall G.N., Solomon D.H. Inhibition of long-acting thyroid stimulator by thyroid particulate fractions. J.Clin. Invest. 45: 552, 1966.
Berumen F.O., Lobsenz I.L., Utiger R.D. Neutralization of the long-acting thyroid stimulator (LATS) by thyroid subcellular fractions. J. Lab. Clin. Med. 70: 640, 1967.
Beall G.N., Doniach D., Roitt I.M., El Kabir D.J. Inhibition of the long-acting thyroid stimulator (LATS) by soluble thyroid fractions. J. Lab. Clin. Med. 73: 988, 1969.
Benhamou-Glynn N., El Kabir D.J., Roitt I.M., Doniach D. Studies on the antigen reacting with the thyroid-stimulating immunoglobulin (LATS) in thyrotoxicosis. Immunology 16: 187, 1969.
Smith B.R. The interaction of the long-acting thyroid stimulator (LATS) with thyroid tissue in vitro. J. Endocrinol. 46: 45, 1970.
Smith B.R., Munro D.S. The nature of the interaction between thyroid stimulating γG-globulin (long acting thyroid stimulator) and thyroid tissue. Biochim. Biophys. Acta 208: 285, 1970.
Chopra I.J., Beall G.N., Solomon D.H. LATS inhibition by a soluble lipoprotein from human thyroid. J. Clin. Endocrinol. Metab. 32: 772, 1971.
Sato S., Noguchi S., Noguchi A. Purification and characterization of long-acting thyroid stimulator inhibiting factor from human thyroid tissues. Biochim. Biophys. Acta 273: 299, 1972.
Dirmikis S., Munro D.S. Comparative studies on the reduction of the response to the long-acting thyroid stimulator by soluble fractions from human, ovine, bovine and porcine thyroids. J. Endocrinol. 59: 579, 1973.
Smith B.R., Hall R. Thyroid-stimulating immunoglobulins in Graves’ disease. Lancet 2: 427, 1974.
Mehdi S.Q., Nussey S.S. A radio-ligand receptor assay for the long-acting thyroid stimulator. Biochem. J. 145: 105, 1975.
Knox A.J.S., von Westarp C., Row V.V., Volpé R. Demonstration of the production of human thyroid-stimulating immunoglobulins (HTSI) by Graves’ lymphocytes cultured in vitro with phytohaemagglutinin (PHA). Metabolism 25: 1217, 1976.
Knox A.J.S., von Westarp C., Row V.V., Volpé R. Thyroid antigen stimulates lymphocytes from patients with Graves’ disease to produce thyroid-stimulating immunoglobulin (TSI). J. Clin. Endocrinol. Metab. 43: 330, 1976.
Mäkinen R., Wagas G., Pekonen F., Apter L., von Willebrand E. Evidence that TSH receptor acts as a mitogenic antigen in Graves’ disease. In: Ann. Endocrinol. (Paris) (8th Annual Meeting of the European Thyroid Association, Lyon, Sept. 27–30,1977), Abstract 148, p. 85A.
Knox A.J.S., von Westarp C., Row V.V., Volpé R. The use of cryopreserved human thyroid tissue for the in in vitro assay of thyroid stimulators. Cryobiology 14: 543, 1977.
DeRobertis E., Pellegrino de Iradi A., Rodriguez de Lores Arnaiz G., Salganicoff L. Cholinergic and non-cholinergic nerve endings in rat brain. I. J. Neurochem. 9: 23, 1962.
Kamath S.A., Rubin E. Interaction of calcium with microsomes: a modified method for the rapid isolation of rat liver microsomes. Biochem. Biophys. Res. Commun. 49: 52, 1972.
Van Herle A.J., Ulier R.P., Matthews N.L., Brown J. Radioimmunoassay for measurement of thyroglobulin in human serum. J.Clin. Invest. 52: 1320, 1973.
Ouchterlony O. Handbook of Immunodiffusion and Immunoelectrophoresis, Ist ed. Ann Arbor Science Publishers Inc., Ann Arbor, Michigan, 1968, p. 21.
Lowry O.H., Rosenbrough N.J., Farr A.L., Randall R.L. Protein measurements with the Folin phenol reagent. J. Biol. Chem. 193: 265, 1951.
Boyum A. Separation of leukocytes from blood and bone marrow. Scand. J. Clin. Lab. Invest. (Suppl. 97) 21: 1, 1968.
Steiner A.L., Kipnis D.M., Utiger R., Parker C. Radioimmunoassay for the measurement of adenosine 3′, 5′-cyclic phosphate. Proc. Natl. Acad. Sei. USA 64: 367, 1969.
Dirmikis S., Munro D.S. Studies on the binding activity for the long-acting thyroid stimulator. J. Endocrinol. 58: 577, 1973.
Mehdi S.Q., Badger J., Kriss J.P. Thyrotropin binding and long-acting thyroid stimulator absorbing activities in subcellular fractions from isolated thyroid cells and thyroid homogenates. Endocrinology 101: 59, 1977.
O’Donnell J., Trokoudes K., Silverberg J., Row V.V., Volpé R. Thyrotropin displacement activity of serum immunoglobulins from patients with Graves’ disease. J. Clin. Endocrinol. Metab. 46: 770, 1978.
Author information
Authors and Affiliations
Additional information
Research Fellows of the Wellesley Hospital Research Foundation
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03350388