Induction of thyroid-stimulating hormone receptor autoimmunity in hamsters.
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 gamma 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.
Ando
Takao
T
Division of Endocrinology, Diabetes, and Bone Diseases, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA. takao.ando@mssm.edu
Imaizumi
Misa
M
Graves
Peter
P
Unger
Pamela
P
Davies
Terry F
TF
D000256:Adenoviridae; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D015551:Autoimmunity / Q000276:immunology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006111:Graves Disease / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000494:pharmacology; D011989:Receptors, Thyrotropin / Q000235:genetics / Q000276:immunology*
D000998:Antiviral Agents; D000949:Histocompatibility Antigens Class II; D011989:Receptors, Thyrotropin; D007371:Interferon-gamma