Graves' animal models of Graves' hyperthyroidism.

Fifty years after the discovery of thyroid autoimmunity, several animal models of Graves' hyperthyroidism are now available. All are inducible types, and diseases are elicited by injecting living cells (professional or nonprofessional antigen-presenting cells) expressing the recombinant thyrotropin receptor (TSHR) or by DNA vaccination with TSHR cDNA in plasmid or adenovirus vectors. Thus most Graves' models are attributed to the cloning of the TSHR cDNA and involve in vivo expression of the TSHR. These breakthroughs have provided us important insights into our understanding of the pathogenesis of Graves' disease, and also indispensable means to exploring the possibility of development of novel therapeutic modalities. In particular, recent studies have begun to scrutinize the genetic factors contributing to the susceptibility to this ailment, and to delineate the roles for central and peripheral tolerance and also for fine balance between autoreactive effector T cells and regulatory T cells in the pathophysiology of anti-TSHR autoimmunity and Graves' hyperthyroidism. Moreover, preliminary, but novel, therapeutic approaches have also been started to treat experimental hyperthyroidism.