This Article Full Text Full Text (PDF) All Versions of this Article: 145/8/3724    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Land, K. J. Articles by Seetharamaiah, G. S. Search for Related Content PubMed PubMed Citation Articles by Land, K. J. Articles by Seetharamaiah, G. S.

Signal Transducer and Activator of Transcription (Stat)-6-Dependent, But Not Stat4-Dependent, Immunity Is Required for the Development of Autoimmunity in Graves’ Hyperthyroidism

Department of Biochemistry and Molecular Biology (K.J.L., J.S.M., G.S.S.), Indiana University School of Medicine, Evansville, Indiana 47712; and Department of Microbiology and Immunology (M.H.K.), Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana 46202

Address all correspondence and requests for reprints to: Dr. Gattadahalli S. Seetharamaiah, Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, 8600 University Boulevard, Evansville, Indiana 47712. E-mail: seethara{at}iupui.edu.

The role of T helper (Th) cells in experimental models of Graves’ hyperthyroidism is still somewhat controversial. To further investigate the role of Th1- and Th2-dependent immunity during the development of Graves’ hyperthyroidism, we tested mice with targeted deletion of signal transducer and activator of transcription-4 (Stat4) or Stat6 genes that, respectively, have impaired Th1 and Th2 immunity. We immunized wild-type BALB/c, Stat4^–/–, or Stat6^–/– mice with human embryonic kidney cells (293 cells) expressing the extracellular domain of human TSH receptor (293-TBP cells). Fifty percent of wild-type BALB/c and Stat4^–/– mice developed Graves’ hyperthyroidism with elevated serum T₄ levels and thyroid stimulatory antibodies. In contrast, Stat6^–/– mice resisted development of the disease. Stat4^–/– mice exhibited a dominant Th2 immune response characterized by the production of IL-4 and IgG1 anti-TSH receptor antibodies. However, Stat6^–/– mice displayed a strong Th1 immune response characterized by the production of interferon- and IgG2a antibodies. Hyperthyroid mice showed enlargement of thyroid glands with hypertrophy and decreased amounts of colloid material, all characteristics of Graves’ disease. These data demonstrate that in this model, Stat6-dependent Th2 immunity is critical for the development of Graves’ hyperthyroidism.

This article has been cited by other articles:

				K. J. Land, P. Gudapati, M. H. Kaplan, and G. S. Seetharamaiah Differential Requirement of Signal Transducer and Activator of Transcription-4 (Stat4) and Stat6 in a Thyrotropin Receptor-289-Adenovirus-Induced Model of Graves' Hyperthyroidism Endocrinology, January 1, 2006; 147(1): 111 - 119. [Abstract] [Full Text] [PDF]

				S. M. McLachlan, Y. Nagayama, and B. Rapoport Insight into Graves' Hyperthyroidism from Animal Models Endocr. Rev., October 1, 2005; 26(6): 800 - 832. [Abstract] [Full Text] [PDF]