Development of an animal model of autoimmune thyroid eye disease.
In previous studies we have transferred thyroiditis to naive BALB/c and NOD mice with human thyrotropin (TSH) receptor (TSHR)-primed splenocytes. Because the TSHR has been implicated in the pathogenesis of thyroid eye disease (TED) we have examined the orbits of recipients of TSHR-primed T cells, generated using a TSHR fusion protein or by genetic immunization. In the NOD mice, 25 of 26 animals treated with TSHR-primed T cells developed thyroiditis with considerable follicular destruction, numerous activated and CD8+ T cells, and immunoreactivity for IFN-gamma. Thyroxine levels were reduced. Thyroiditis was not induced in controls. None of the NOD animals developed any orbital pathology. Thirty-five BALB/c mice received TSHR-primed spleen cells. Thyroiditis was induced in 60-100% and comprised activated T cells, B cells, and immunoreactivity for IL-4 and IL-10. Autoantibodies to the receptor were induced, including TSH binding inhibiting Igs. A total of 17 of 25 BALB/c orbits displayed changes consisting of accumulation of adipose tissue, edema caused by periodic acid Schiff-positive material, dissociation of the muscle fibers, the presence of TSHR immunoreactivity, and infiltration by lymphocytes and mast cells. No orbital changes or thyroiditis were observed in control BALB/c mice. We have induced orbital pathology having many parallels with human TED, only in BALB/c mice, suggesting that a Th2 autoimmune response to the TSHR may be a prerequisite for the development of TED.
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Department of Histology, Louvain Medical School, and Institut de Recherche en Biologie Humaine et Nucleaire, Universite Libre de Bruxelles, Brussels, Belgium.
Costagliola
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Detrait
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Denef
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Vassart
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Ludgate
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D000818:Animals; D001666:Binding Sites, Antibody; D002352:Carrier Proteins / Q000235:genetics; D004195:Disease Models, Animal; D005128:Eye Diseases / Q000209:etiology / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000097:blood; D017710:Lymphocyte Transfusion; D058619:Maltose-Binding Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D009915:Orbit / Q000473:pathology; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000637:transplantation; D013961:Thyroid Gland / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood; D013967:Thyroiditis, Autoimmune / Q000209:etiology / Q000276:immunology* / Q000473:pathology*
D002352:Carrier Proteins; D018828:Immunoglobulins, Thyroid-Stimulating; D058619:Maltose-Binding Proteins; D011989:Receptors, Thyrotropin; D013963:Thyroid Hormones