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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; and
Department of Pathology, University of Wales College of Medicine, Cardiff, United Kingdom
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-
. 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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