IMMUNOTOXIC EFFECTS OF IODINE

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DESCRIPTION: (Adapted from the investigator's Abstract) Autoimmune thyroiditis is a multifactorial condition with several genetic and environmental components contributing to disease. Iodine has been implicated as one of these components. The broad long-term objectives remain to explore the immunotoxic of iodine in autoimmune thyroiditis (AT). Increased environmental exposure to iodine from dietary or therapeutic sources may contribute to the increasing prevalence of AT in humans. Both animal models of thyroiditis and clinical observations in humans relate ingestion of excess iodine as a potent risk factor in subjects genetically predisposed to AT. However, the pathogenic mechanism has not been determined. The investigator's hypothesis is that excess ingested iodine leads to highly iodinated Tg, and that the highly iodinated Tg is a more potent auto-immunogen than poorly-iodinated Tg in subjects predisposed to AT. As a new direction from their current research on humans, they will use a mouse model as the primary test system to study the role of iodine in triggering the expression of AT. The congenic mutant strain of NOD mice (NOD.B10.A (4R)-H2-H4) do not get diabetes but do get thyroiditis that is exacerbated by dietary iodine. The investigator will continue to study the role of iodinated Tg in humans using in vitro cell techniques. The specific aims for this proposal are: 1. To show that ingested iodine promotes AT in the NOD mouse model and establish basic and immunological parameters. The investigator will study the effect of iodine dose, timing, age, sex, on disease induction, on phenotype of cells in the thyroid. He will determine the frequency of these cells and then relate these findings to their cytokine and antibody profiles. 2. To induce thyroiditis in vivo. He will show that T cells from mice with lesions after a high iodine diet will transfer disease into non-affect recipients, first, with spleen cells from iodine-treated mice, then iodinated Tg to support the hypothesis. Individual parameters of the immune system will be monitored as for specifics aim 1. 3. To show in human studies that T cell clones preferentially recognize highly iodinated Tg greater than poorly iodinated Tg, to establish frequency of these cells by limiting dilution and determine their cytokine profiles in order to relate these findings to disease. The mouse model permits mechanistic research of dietary iodine that is closely analogous to humans and allows experimental procedures that cannot be done in humans. If the mechanism of disease can be clarified, then the potential exists for developing strategies to abrogate the deleterious immune response.