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.
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