INDUCTION OF GRAVES-LIKE DISEASE IN MICE BY IMMUNIZATION WITH FIBROBLASTS TRANSFECTED WITH THE THYROTROPIN RECEPTOR AND A CLASS-II MOLECULE

Graves disease is an autoimmune thyroid disease characterized by the p resence of antibodies against the thyrotropin receptor (TSHR), which s timulate the thyroid to cause hyperthyroidism and/or goiter. By immuni zing mice with fibroblasts transfected with both the human TSHR and a major histocompatibility complex class II molecule, but not by either alone, we have induced immune hyperthyroidism that has the major humor al and histological features of Graves disease: stimulating TSHR antib odies, thyrotropin binding inhibiting immunoglobulins, which are diffe rent from the stimulating TSHR antibodies, increased thyroid hormone l evels, thyroid enlargement, thyrocyte hypercellularity, and thyrocyte intrusion into the follicular lumen. The results suggest that the aber rant expression of major histocompatibility complex class II molecules on cells that express a native form of the TSHR can result in the ind uction of functional anti-TSHR antibodies that stimulate the thyroid. They additionally suggest that the acquisition of antigen-presenting a bility on a target cell containing the TSHR can activate T and B cells normally present in an animal and induce a disease with the major fea tures of autoimmune Graves.