Animal Models of Autoimmune Thyroid Disease

SummaryAutoimmune thyroid diseases (AITD) cover the spectrum from hypothyroid Hashimoto’s thyroiditis (HT) to hyperthyroid Graves’ disease (GD). The main autoimmune targets are thyroglobulin (TG), thyroid peroxidase (TPO) and the thyrotropin receptor (TSHR). Autoantibodies and specific T cells directed against all three autoantigens can be detected in the circulation of HT and GD patients and also in a significant proportion of the healthy population. In AITD, as in other autoimmune conditions, the central question remains how is immune tolerance overcome? In vivo models, mostly induced in rodents, have contributed to our understanding of the mechanisms operating and many hundreds of papers, spanning from 1956 to the present day, have been published describing the results obtained. Most of the information has been derived from experimental autoimmune thyroiditis (EAT) models induced with TG, an antigen that, based on current knowledge, seems to be of lesser importance in human AITD. Nevertheless, many of the basic precepts underlying autoimmunity, for example the importance of the major histocompatability complex (MHC) II and the existence of immunoregulatory T cells, have been identified using TG-based models, and these are described. Reports based on induction of disease with TPO, the driving antigen in HT, are not very numerous but include a seminal paper that clearly demonstrates the redundancy of autoantibodies and the central role of T cells in pathogenesis. In contrast, autoantibodies to the TSHR cause GD and much of the chapter is devoted to models attempting to mimic GD, and these have been the subject of considerable effort since its cloning in 1998. This has culminated with the recent publication of monoclonal antibodies with thyroid stimulating activity (TSAB) either measured in vitro or in vivo.