TSH receptor-adenovirus-induced Graves’ hyperthyroidism is attenuated in both interferon-γand interleukin-4 knockout mice; implications for the Th1/Th2 paradigm
| Autor: | H. Kano, Y. Kumazawa, O. Saitoh, Sandra M. McLachlan, Basil Rapoport, Yuji Nagayama |
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| Rok vydání: | 2004 |
| Předmět: |
endocrine system
medicine.medical_specialty endocrine system diseases medicine.medical_treatment Immunology Antineoplastic Agents Antiviral Agents Adenoviridae Interferon-gamma Mice Viral Proteins Th2 Cells Internal medicine Splenocyte medicine Animals Immunology and Allergy Interferon gamma Receptor Interleukin 4 Autoantibodies Mice Knockout Mice Inbred BALB C biology business.industry Thyroid Receptors Thyrotropin T-Lymphocytes Helper-Inducer Th1 Cells Graves Disease eye diseases Thyroxine medicine.anatomical_structure Endocrinology Cytokine Immunoglobulin G Knockout mouse Animal Studies biology.protein Female Interleukin-4 Antibody business hormones hormone substitutes and hormone antagonists Immunoglobulins Thyroid-Stimulating medicine.drug |
| Zdroj: | Clinical and Experimental Immunology. 138:417-422 |
| ISSN: | 1365-2249 0009-9104 |
| DOI: | 10.1111/j.1365-2249.2004.02641.x |
| Popis: | SUMMARYThe role of the Th1/Th2 balance in the pathogenesis of murine Graves’ hyperthyroidism is controversial. In BALB/c mice injected with adenovirus expressing TSH receptor (TSHR-adeno model), we found that suppression of TSHR-specific Th1 immune responses by exogenous interleukin-4 (IL-4), α-galactosylceramide or helminth (Schistosoma mansoni) infection was associated with inhibition of hyperthyroidism, indicating the critical role for Th1 cytokines. In contrast, BALB/c IL-4 knockout (KO), but not interferon-γ (IFN-γ) KO mice failed to develop Graves’ hyperthyroidism when injected with TSHR-expressing M12 B lymphoma cells (TSHR-M12 model), suggesting the importance of Th2 cytokine IL-4. To reconcile differences in these two models, we used IL-4 KO and IFN-γ KO BALB/c mice in the TSHR-adeno model. Unlike wild-type (wt) BALB/c mice in which 60% developed hyperthyroidism, only 13 and 7% of IL-4 KO and IFN-γ KO mice, respectively, became hyperthyroid. Thyroid stimulating antibodies were positive in most hyperthyroid mice. TSHR antibody titres determined by TSH binding inhibition and ELISA were comparable in all three groups. IgG1 and IgG2a TSHR antibody titres were similar in IFN-γ KO and wt mice, whereas IgG1 TSHR antibody titres and TSHR-specific splenocyte IFN-γ secretion were lower in IL-4 KO than in IFN-γ KO and wt mice, respectively. Our results clearly implicate both IFN-γ and IL-4 in development of hyperthyroidism in the TSHR-adeno model. These data, together with the previous report, also indicate different cytokine requirements in these two Graves’ models, with IFN-γ being more important in the TSHR-adeno than the TSHR-M12 model. Moreover, our previous and present observations indicate a difference in the role of exogenous versus endogenous IL-4 in TSHR-adenovirus induced Graves’ hyperthyroidism. |
| Databáze: | OpenAIRE |
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