The broad objective of the proposed research is to study the mechanism by which iodine induces autoimmune thyroiditis in the susceptible animal and human population. Specifically, the hypotheses that thyroglobulin, a thyroid specific protein, is non-immunogenic in the poorly iodinated state but becomes highly immunogenic upon iodination will be tested in the proposed studies. Obese strain (OS) chickens which spontaneously develop severe thyroiditis early in life and in which the disease is prevented by stringent iodine depletion will be utilized as an animal model. Iodinated and poorly iodinated thyroglobulin will be compared for their ability to induce disease in OS chickens in which spontaneous disease has been prevented by an iodine depletion regimen. These thyroglobulin preparations will also be compared for ability to prime donor OS T cells in adoptive transfer experiments and for stimulation of OS lymphocytes in vitro. Iodinated thyroglobulin from OS and normal chicken strains will also be compared in the above experiments since structural differences may account for the immunogenicity of OS iodinated thyroglobulin. Iodine content of serum thyroglobulin will be compared in OS and normal strains to examine the possibility that serum Tg, normally poorly iodinated, may be more iodinated in the OS on a regular iodine diet Finally, T cell lines and clones specifically reactive to iodinated OS thyroglobulin will be developed and tested for the ability to produce disease upon transfer to recipients or to vaccinate against spontaneous disease. These studies in the chicken model should provide greater understanding of the role of iodine in the etiology of human autoimmune thyroiditis.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Endocrinology Study Section (END)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Wayne State University
Schools of Medicine
United States
Zip Code
Brown, T R; Zhao, G; Palmer, K C et al. (1998) Thyroid injury, autoantigen availability, and the initiation of autoimmune thyroiditis. Autoimmunity 27:1-12
Sundick, R S; Bagchi, N; Brown, T R (1996) The obese strain chicken as a model for human Hashimoto's thyroiditis. Exp Clin Endocrinol Diabetes 104 Suppl 3:4-6
Bagchi, N; Sundick, R S; Hu, L H et al. (1996) Distinct regions of thyroglobulin control the proliferation and suppression of thyroid-specific lymphocytes in obese strain chickens. Endocrinology 137:3286-90
Bagchi, N; Brown, T R; Sundick, R S (1995) Thyroid cell injury is an initial event in the induction of autoimmune thyroiditis by iodine in obese strain chickens. Endocrinology 136:5054-60