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. Beca use the TSHR has been implicated in the pathogenesis of thyroid eye disease (TED) we hare examined the orbits of recipients of TSHR-primed T cells, ge nerated using a TSAR fusion protein or by genetic immunization. In the NOD mice, 25 of 26 animals treated with TSHR-primed T cells developed thyroidit is 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 an! orbital pathology. Thirty-five BALB/c mice received TSHR-primed spleen cells. Thyroiditis was induced in 60-100% and comprised activated T cells, a cells, and immunoreactivity for IL-4 and IL-10. Autoantibodies to the re ceptor were induced, including TSH binding inhibiting Igs. A total of 17 of 25 BALB/c orbits displayed changes consisting of accumulation of adipose t issue, edema caused by periodic acid Schiff-positive material, dissociation of the muscle fibers, the presence of TSHR immunoreactivity, and infiltrat ion by lymphocytes and mast cells. No orbital changes or thyroiditis were o bserved in control BALB/c mice. We have induced orbital pathology haring ma ny parallels with human TED, only in BALB/c mice, suggesting that a Th2 aut oimmune response to the TSHR may be a prerequisite for the development of T ED.