{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:00:27Z","timestamp":1791104427026,"version":"4.1.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2004,8,1]],"date-time":"2004-08-01T00:00:00Z","timestamp":1091318400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Graves\u2019 hyperthyroidism, an organ-specific autoimmune disease mediated by stimulatory thyrotropin receptor (TSHR) autoantibodies, has been considered a Th2-dominant disease. However, recent data with mouse Graves\u2019 models are conflicting. For example, we recently demonstrated that injection of BALB\/c mice with adenovirus coding the TSHR induced Graves\u2019 hyperthyroidism characterized by mixed Th1 and Th2 immune responses against the TSHR, and that transient coexpression of the Th2 cytokine IL-4 by adenovirus skewed Ag-specific immune response toward Th2 and suppressed disease induction. To gain further insight into the relationship between immune polarization and Graves\u2019 disease, we evaluated the effect of Th2 immune polarization by helminth Schistosoma mansoni infection and \u03b1-galactosylceramide (\u03b1-GalCer), both known to bias the systemic immune response to Th2, on Graves\u2019 disease. S. mansoni infection first induced mixed Th1 and Th2 immune responses to soluble worm Ags, followed by a Th2 response to soluble egg Ags. Prior infection with S. mansoni suppressed the Th1-type anti-TSHR immune response, as demonstrated by impaired Ag-specific IFN-\u03b3 secretion of splenocytes and decreased titers of IgG2a subclass anti-TSHR Abs, and also prevented disease development. Similarly, \u03b1-GalCer suppressed Ag-specific splenocyte secretion of IFN-\u03b3 and prevented disease induction. However, once the anti-TSHR immune response was fully induced, S. mansoni or \u03b1-GalCer was ineffective in curing disease. These data support the Th1 theory in Graves\u2019 disease and indicate that suppression of the Th1-type immune response at the time of Ag priming may be crucial for inhibiting the pathogenic anti-TSHR immune response.<\/jats:p>","DOI":"10.4049\/jimmunol.173.3.2167","type":"journal-article","created":{"date-parts":[[2014,4,22]],"date-time":"2014-04-22T23:38:25Z","timestamp":1398209905000},"page":"2167-2173","source":"Crossref","is-referenced-by-count":88,"title":["<i>Schistosoma mansoni<\/i>\n                    and \u03b1-Galactosylceramide: Prophylactic Effect of Th1 Immune Suppression in a Mouse Model of Graves\u2019 Hyperthyroidism"],"prefix":"10.1093","volume":"173","author":[{"given":"Yuji","family":"Nagayama","sequence":"first","affiliation":[{"name":"Department of Medical Gene Technology, Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, Nagasaki University , Nagasaki ,","place":["Japan"]},{"name":"Department of Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University , Nagasaki ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanji","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Institute of Tropical Medicine, Nagasaki University , Nagasaki ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masami","family":"Niwa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Graduate School of Biomedical Sciences, Nagasaki University , Nagasaki ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra M","family":"McLachlan","sequence":"additional","affiliation":[{"name":"Autoimmune Disease Unit, Cedars-Sinai Research Institute and School of Medicine, University of California , Los Angeles, CA 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basil","family":"Rapoport","sequence":"additional","affiliation":[{"name":"Autoimmune Disease Unit, Cedars-Sinai Research Institute and School of Medicine, University of California , Los Angeles, CA 90048"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2004,8,1]]},"reference":[{"key":"2026020212085384000_R1","first-page":"673","volume-title":"Endocr. Rev.","year":"1998"},{"key":"2026020212085384000_R2","first-page":"2789","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020212085384000_R3","first-page":"3522","volume-title":"J. Immunol.","year":"2003"},{"key":"2026020212085384000_R4","first-page":"2195","volume-title":"J. Immunol.","year":"2003"},{"key":"2026020212085384000_R5","first-page":"1626","volume-title":"Science","year":"1997"},{"key":"2026020212085384000_R6","first-page":"353","volume-title":"Tissue Antigens","year":"2002"},{"key":"2026020212085384000_R7","first-page":"211","volume-title":"Nat. Rev. Immunol.","year":"2003"},{"key":"2026020212085384000_R8","first-page":"2373","volume-title":"J. Immunol.","year":"1999"},{"key":"2026020212085384000_R9","first-page":"2014","volume-title":"Eur. J. Immunol.","year":"1999"},{"key":"2026020212085384000_R10","first-page":"11931","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1995"},{"key":"2026020212085384000_R11","first-page":"1163","volume-title":"J. Exp. Med.","year":"1995"},{"key":"2026020212085384000_R12","first-page":"2989","volume-title":"Eur. J. Immunol.","year":"1996"},{"key":"2026020212085384000_R13","first-page":"1047","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026020212085384000_R14","first-page":"177","volume-title":"Nature","year":"1998"},{"key":"2026020212085384000_R15","first-page":"4375","volume-title":"J. Immunol.","year":"2000"},{"key":"2026020212085384000_R16","first-page":"144","volume-title":"Clin. Immunol.","year":"2001"},{"key":"2026020212085384000_R17","first-page":"1831","volume-title":"J. Exp. Med.","year":"1998"},{"key":"2026020212085384000_R18","first-page":"6007","volume-title":"J. Immunol.","year":"2002"},{"key":"2026020212085384000_R19","first-page":"119","volume-title":"Gastroenterology","year":"2000"},{"key":"2026020212085384000_R20","first-page":"1052","volume-title":"Nat. Med.","year":"2001"},{"key":"2026020212085384000_R21","first-page":"1057","volume-title":"Nat. Med.","year":"2001"},{"key":"2026020212085384000_R22","first-page":"13838","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2001"},{"key":"2026020212085384000_R23","first-page":"313","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2026020212085384000_R24","first-page":"662","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020212085384000_R25","first-page":"1801","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2026020212085384000_R26","first-page":"1789","volume-title":"J. Exp. Med.","year":"2001"},{"key":"2026020212085384000_R27","first-page":"1830","volume-title":"Eur. J. Immunol.","year":"2003"},{"key":"2026020212085384000_R28","first-page":"6777","volume-title":"Proc. Natl. Acad. Sci. USA","year":"2001"},{"key":"2026020212085384000_R29","first-page":"101","volume-title":"Immunol. Lett.","year":"2002"},{"key":"2026020212085384000_R30","first-page":"67","volume-title":"Mechanisms and Lymphocyte Activation and Immune Regulation, Vol. VII: Molecular Determinants of Microbial Immunity","year":"1998"},{"key":"2026020212085384000_R31","first-page":"1322","volume-title":"J. Immunol.","year":"1991"},{"key":"2026020212085384000_R32","first-page":"159","volume-title":"J. Exp. Med.","year":"1991"},{"key":"2026020212085384000_R33","first-page":"3264","volume-title":"J. Immunol.","year":"1992"},{"key":"2026020212085384000_R34","first-page":"3050","volume-title":"Eur. J. Immunol.","year":"1994"},{"key":"2026020212085384000_R35","first-page":"769","volume-title":"J. Exp. Med.","year":"1995"},{"key":"2026020212085384000_R36","first-page":"2251","volume-title":"J. Biol. Chem.","year":"1992"},{"key":"2026020212085384000_R37","first-page":"169","volume-title":"Parasitol. Immunol.","year":"1999"},{"key":"2026020212085384000_R38","first-page":"1439","volume-title":"Eur. J. Immunol.","year":"2003"},{"key":"2026020212085384000_R39","first-page":"59","volume-title":"Int. Immunol.","year":"2003"},{"key":"2026020212085384000_R40","first-page":"477","volume-title":"Clin. Exp. Immunol.","year":"2000"},{"key":"2026020212085384000_R41","first-page":"311","volume-title":"Exp. Parasitol.","year":"1991"},{"key":"2026020212085384000_R42","first-page":"488","volume-title":"J. Exp. Med.","year":"1970"},{"key":"2026020212085384000_R43","first-page":"5678","volume-title":"Proc. Natl. Acad. Sci. USA","year":"1988"},{"key":"2026020212085384000_R44","first-page":"1287","volume-title":"J. Clin. Endocrinol. Metab.","year":"2001"},{"key":"2026020212085384000_R45","first-page":"725","volume-title":"Immunity","year":"2002"},{"key":"2026020212085384000_R46","first-page":"6058","volume-title":"Infect. Immun.","year":"2002"},{"key":"2026020212085384000_R47","first-page":"4857","volume-title":"J. Immunol.","year":"1993"},{"key":"2026020212085384000_R48","first-page":"447","volume-title":"J. Immunol.","year":"2003"},{"key":"2026020212085384000_R49","first-page":"241","volume-title":"Parasite Immunol.","year":"1998"},{"key":"2026020212085384000_R50","first-page":"1599","volume-title":"Infect. Immun.","year":"1999"},{"key":"2026020212085384000_R51","first-page":"623","volume-title":"Int. Immunol.","year":"2000"},{"key":"2026020212085384000_R52","first-page":"1291","volume-title":"Microbes Infect.","year":"2002"},{"key":"2026020212085384000_R53","first-page":"198","volume-title":"Immunol. Today","year":"1992"},{"key":"2026020212085384000_R54","first-page":"169","volume-title":"Clin. Immunol. Immunopathol.","year":"1994"},{"key":"2026020212085384000_R55","first-page":"1434","volume-title":"Eur. J. Immunol.","year":"1994"},{"key":"2026020212085384000_R56","first-page":"10","volume-title":"J. Neuroimmunol.","year":"2001"},{"key":"2026020212085384000_R57","first-page":"305","volume-title":"J. Exp. Med.","year":"1994"},{"key":"2026020212085384000_R58","first-page":"1164","volume-title":"J. Immunol.","year":"2001"},{"key":"2026020212085384000_R59","first-page":"723","volume-title":"J. Clin. Invest.","year":"1990"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/173\/3\/2167\/62610178\/2167.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/173\/3\/2167\/62610178\/2167.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T17:10:00Z","timestamp":1770052200000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/173\/3\/2167\/8035426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,8,1]]},"references-count":59,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2004,8,1]]},"published-print":{"date-parts":[[2004,8,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.173.3.2167","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2004,8]]},"published":{"date-parts":[[2004,8,1]]}}}