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*THYROGLOBULIN
The Journal of Immunology, 2002, 168: 2470-2474.
Copyright © 2002 by The American Association of Immunologists

A Unique Combination of Inflammatory Cytokines Enhances Apoptosis of Thyroid Follicular Cells and Transforms Nondestructive to Destructive Thyroiditis in Experimental Autoimmune Thyroiditis1

Su He Wang, James D. Bretz, Ellen Phelps, Emese Mezosi, Patricia L. Arscott, Saho Utsugi and James R. Baker, Jr.2

Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109

Treatment of cultured primary human thyroid cells with IFN-{gamma} and TNF-{alpha} uniquely allows the induction of Fas-mediated apoptosis. To investigate the role of this cytokine combination in vivo, CBA/J mice were immunized with thyroglobulin and then injected with IFN-{gamma} and TNF-{alpha}. Compared with control animals, mice treated with IFN-{gamma} and TNF-{alpha} showed significantly sustained lymphocytic infiltration in the thyroid, which was associated with the destruction of portions of the follicular architecture at wk 6 after initial immunization. Furthermore, the number of apoptotic thyroid follicular cells was increased only in the thyroids from mice treated with the IFN-{gamma} and TNF-{alpha}. We also analyzed the function of the Fas pathway in vivo in cytokine-treated mice by using an agonist anti-Fas Ab injected directly into the thyroid. Minimal apoptosis of thyroid epithelial cells was observed unless the mice were pretreated with IFN-{gamma} and TNF-{alpha}. These data demonstrate that this unique combination of inflammatory cytokines facilitates the apoptotic destruction of thyroid follicular cells in experimental autoimmune thyroiditis, in a manner similar to what is observed in Hashimoto’s thyroiditis in humans.




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