1998 Fiscal Year Final Research Report Summary
Study on mechanisms of induction of anti-thyrotropin receptor antibodies in murine experimental Graves'disease.
| Project/Area Number |
09670468
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | Chiba University School of Medicine |
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Principal Investigator |
KOHNO Yoichi School of Medicine Chiba University, Professor, 医学部, 教授 (60161882)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Graves'disease / mouse model / anti-thyrotropin receptor antibodies / epitope / costimulatory molecule / 副刺激分子 / エピトープ |
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| Research Abstract |
In order to investigate the mechanisms of induction of anti-thyrotropin receptor antibodies in Graves' disease, we established a new mouse model presenting stimulating anti-thyrotropin receptor-mediated hyperthyroidism with similar features of Graves' disease in human in which fibroblasts transfected with human thyrotropin receptor gene as an immunogen, The study showed that stimulating anti- thyrotropin receptor antibodies is exclusively dependent on the expression of class IT MHC molecule on the thyrotropin receptor-expressing fibroblasts used for immunization although total level of anti- thyrotropin receptor antibodies is influenced by some gene(s) other than MHC.These results strongly suggest that aberrant expression of class II MHC molecule on target organ (in this case, thyroid follicular cells) is quite important for initiation or progression of autoimmunity. By use of fibroblasts transfected with chimera receptors between human thyrotropin receptor and rat lutenizing hormone/chorionic gonadotropin receptor, we further demonstrated that N-terminal portion of the thyrotropin is crucial in induction of anti-thyrotropin receptor. Finally, we introduced CD86 gene into murine fibroblasts and immunized mice with thyrotropin receptor-positive fibroblasts which as higher costimulatory capacity for T cells. The results indicated in this system that CD86 has no additive effect on induction of anti-thyrotropin receptor antibodies.
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