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Induction of Thyroid-Stimulating Hormone Receptor Autoimmunity in Hamsters

Division of Endocrinology, Diabetes, and Bone Diseases, Departments of Medicine (T.A., M.I., P.G., T.F.D.) and Pathology (P.U.), Mount Sinai School of Medicine, New York, New York 10029

Address all correspondence and requests for reprints to: Takao Ando, M.D., Mount Sinai School of Medicine, Box 1055, 1 Gustave L. Levy Place, New York, New York 10029. E-mail: takao.ando{at}mssm.edu.

Female Chinese hamsters (n = 10) were immunized with Chinese hamster ovary (CHO) cells that expressed the human TSH receptor (TSHR) to generate a model of Graves’ disease. TSHR-autoantibodies (TSHR-Ab) were determined by CHO-TSHR. Two hamsters with stimulating TSHR-Ab showed thyrocyte hypertrophy associated with a focal lymphocytic infiltration. CHO-TSHR were then stimulated with interferon to enhance major histocompatibility complex class II expression. However, after immunization no stimulating TSHR-Ab were detected, but blocking TSHR-Ab were found in three of five animals. The thyroid glands from these hamsters showed marked thinning of thyroid epithelial cells, indicative of early thyroid atrophy consistent with a TSHR blocking antibody, but no lymphocytic infiltration. Lastly, female Armenian hamsters were immunized with an adenovirus construct incorporating wild-type TSHR. High titers of TSHR-Ab were induced effectively, but the thyroid hypertrophy observed was not associated with a lymphocyte infiltration.

In summary, we demonstrated that the hamster could serve as a model of TSHR autoimmunity and that an adenoviral vector produced higher levels of TSHR-Ab than more conventional immunization with cells. The data also indicated that the intrathyroidal cellular immunity in this model was not related to TSHR-Ab formation and was an independent reflection of the T-cell immune response to TSHR antigen.

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