A great deal of circumstantial evidence has linked
iodine with the rising incidence of
autoimmune thyroiditis in the United States. In our investigations, we have shown directly that T cells from humans with
chronic lymphocytic thyroiditis proliferate in the presence of iodinated but not in the presence of noniodinated human
thyroglobulin. Moreover, the proliferative response is restored when the
thyroglobulin is iodinated artificially in vitro. Using a panel of
monoclonal antibodies, we found evidence that the presence of
iodine induces a number of stereochemical changes in the conformation of the molecule, resulting in the loss of some
antigenic determinants and the appearance of others. One prominent determinant was associated with the
iodine-containing
amino acid thyroxine. Both the number and position of the
iodine substituents determine the precise specificity of this
epitope. A new model for the study of the role of
iodine in inducing thyroid autoimmunity has become available in the form of the nonobese diabetic (NOD)-H2(h4) mouse. This animal develops
autoimmune thyroiditis spontaneously but in relatively low prevalence. However, if
iodine is added to the
drinking water, the prevalence and severity of the thyroid lesions increase markedly. The immune response is specific for
thyroglobulin, both in terms of the antibody response and T-cell proliferation. In fact, the appearance of lesions can be predicted by the presence of
thyroglobulin-specific
IgG2b antibody. The disease, moreover, can be transferred adoptively, using spleen cells from
iodine-fed donors treated in vitro with iodinated
thyroglobulin. The effects of
iodine feeding are greater in conventional animals compared with those maintained under specific pathogen-free conditions. Based on T-cell proliferation, it appears that the NOD-H2(h4) strain of mice has innately a greater response to murine
thyroglobulin than do other mouse strains and that the proliferation is increased even more by feeding
iodine. We suggest, therefore, that the presence of
iodine increases the autoantigenic potency of
thyroglobulin, a major pathogenic
antigen in the induction of
autoimmune thyroiditis. This animal model provides a unique opportunity for investigating in detail the mechanisms by which an environmental agent can trigger a pathogenic autoimmune response in a susceptible host.