Schistosoma mansoni and α-galactosylceramide:: Prophylactic effect of Th1 immune suppression in a mouse model of Graves' hyperthyroidism

被引:84
作者
Nagayama, Y
Watanabe, K
Niwa, M
McLachlan, SM
Rapoport, B
机构
[1] Nagasaki Univ, Grad Sch Biomed Sci, Atom Bomb Dis Inst, Dept Med Gene Technol, Nagasaki 8528523, Japan
[2] Nagasaki Univ, Grad Sch Biomed Sci, Dept Pharmacol, Nagasaki 8528523, Japan
[3] Nagasaki Univ, Inst Trop Med, Dept Parasitol, Nagasaki 8528523, Japan
[4] Univ Calif Los Angeles, Cedars Sinai Res Inst, Autoimmune Dis Unit, Los Angeles, CA 90048 USA
[5] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90048 USA
关键词
D O I
10.4049/jimmunol.173.3.2167
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Graves' 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' models are conflicting. For example, we recently demonstrated that injection of BALB/c mice with adenovirus coding the TSHR induced Graves' 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' disease, we evaluated the effect of Th2 immune polarization by helminth Schistosoma mansoni infection and alpha-galactosylceramide (alpha-GalCer), both known to bias the systemic immune response to Th2, on Graves' 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-gamma secretion of splenocytes and decreased titers of IgG2a subclass anti-TSHR Abs, and also prevented disease development. Similarly, alpha-GalCer suppressed Ag-specific splenocyte secretion of IFN-gamma and prevented disease induction. However, once the anti-TSHR immune response was fully induced, S. mansoni or alpha-GalCer was ineffective in curing disease. These data support the Th1 theory in Graves 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.
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页码:2167 / 2173
页数:7
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