The role of iodine in experimental autoimmune thyroiditis

Li, Haiyan S. (2006) The role of iodine in experimental autoimmune thyroiditis. Doctoral (PhD) thesis, Memorial University of Newfoundland.

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Abstract

Experimental autoimmune thyroiditis (EAT), a murine model of Hashimoto's thyroiditis in humans, is a T cell-mediated autoimmune disease, characterized by destruction of thyroid follicles by infiltrating inflammatory cells. Immunization with thyroglobulin (Tg) – one of the major thyroid autoantigens – or Tg peptides in complete Freund's adjuvant is the classical way to elicit EAT in susceptible mouse strains. -- The first part of the thesis investigates the critical role of iodine in the immunopathogenicity of Tg. I have delineated three iodotyrosyl-containing peptides (aa.117-132, 304-318, and 1931-1945) which are not immunogenic in their native form but become immunopathogenic in their iodinated form. Iodination of tyrosyls facilitates either peptide binding to MHC or T-cell recognition of the peptide. In addition, iodotyrosyl formation has increasing, neutral or decreasing effects on the immunogenic profiles of other three Tg peptides (a.a. 179-194, 2529-2545, and 2540-2554) which are immunogenic in their non-iodinated forms. In a parallel study, I attempt to generate highly iodinated Tg in vivo via NaI administration in the drinking water of mice. We found that this regimen did not facilitate the generation of highly iodinated Tg in vivo, but elicited goitres hypothyroidism in SJL but not CBA/J mice. The mechanisms behind this phenomenon remain poorly understood, but it does not seem to have an autoimmune basis.

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