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J Immunol ; 162(8): 4966-74, 1999 Apr 15.
Article in English | MEDLINE | ID: mdl-10202044

ABSTRACT

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.


Subject(s)
Eye Diseases/immunology , Eye Diseases/pathology , Thyroiditis, Autoimmune/immunology , Thyroiditis, Autoimmune/pathology , Animals , Binding Sites, Antibody , Carrier Proteins/genetics , Disease Models, Animal , Eye Diseases/etiology , Female , Humans , Immunoglobulins, Thyroid-Stimulating/blood , Lymphocyte Transfusion , Maltose-Binding Proteins , Mice , Mice, Inbred BALB C , Mice, Inbred NOD , Orbit/pathology , Receptors, Thyrotropin/genetics , Receptors, Thyrotropin/immunology , T-Lymphocytes/transplantation , Thyroid Gland/pathology , Thyroid Hormones/blood , Thyroiditis, Autoimmune/etiology
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