Iodination of murine thyroglobulin enhances autoimmune reactivity in the NOD.H2 mouse.
Autoimmune thyroiditis in humans has been linked to excess iodine intake. A causative relationship between dietary iodine and thyroiditis has been clearly established in animal models of thyroiditis, including the NOD.H2(h4) mouse strain, which develops enhanced thyroiditis spontaneously after supplementation of drinking water with sodium iodide. To assess the mechanisms by which iodine may contribute to disease pathogenesis, we have purified hypoiodinated thyroglobulin (Lo-I Tg) from the thyroids of mice fed methimazole and potassium perchlorate. This preparation contained only a trace of iodine and was poorly reactive to monoclonal antibody 42C3, which has been shown previously to distinguish hypoiodinated from normal Tg. A cloned T cell line 2D11 from a diseased NOD.H2(h4) mouse proliferated in response to normal Tg, but not to Lo-I Tg. Serum antibodies from NOD.H2(h4) mice with thyroiditis were poorly reactive to Lo-I Tg. To determine that these changes were due specifically to iodine content, Lo-I Tg was reiodinated in vitro. Reiodination of Lo-I Tg partially re-established the reactivity of NOD.H2(h4) serum antibodies. The data demonstrate that the reactivity of thyroglobulin-specific antibodies and certain T cells are dependent on the iodine content of thyroglobulin. These findings suggest that iodine contributes to autoimmune thyroiditis in the NOD.H2(h4) mouse by directly enhancing the antigenicity of thyroglobulin.
Barin
J G
JG
Johns Hopkins University School of Medicine, Department of Pathology, Baltimore, MD 21205, USA.
Talor
M V
MV
Sharma
R B
RB
Rose
N R
NR
Burek
C L
CL
D000375:Aging / Q000276:immunology; D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation; D007455:Iodine / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000276:immunology; D013954:Thyroglobulin / Q000276:immunology*; D013967:Thyroiditis, Autoimmune / Q000276:immunology* / Q000473:pathology
D001323:Autoantibodies; D013954:Thyroglobulin; D007455:Iodine