グルタミン酸脱炭酸酵素 (GAD) 及びプロインスリンを用いた1型糖尿病に対するワクチン療法の試み

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  • グルタミンサン ダツタンサン コウソ GAD オヨビ プロインスリン オ モチイタ 1ガタ トウニョウビョウ ニ タイスル ワクチン リョウホウ ノ ココロミ
  • Vaccination with Glutamic Acid Decarboxylase (GAD) or Proinsulin against Type 1 Diabetes Mellitus

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Abstract

To evaluate the effect of vaccination by islet-antigen-expressing cells on type 1 diabetes, we utilized recombinant adenovirus vectors transducing several islet-antigen genes into NOD fibroblasts and tried to modify the development of autoimmune diabetes in NOD mice, an excellent animal model of human type 1 diabetes. The expression of GAD67 or proinsulin II was detected in NOD fibroblasts transfected with Ad. mGAD67 or Ad. mPreproinsulin II by western blotting or ELISA, respectively. The transfected NOD fibroblasts were subcutaneously transplanted to young female NOD mice. Diabetic incidence was apparently reduced in NOD mice transplanted with either Ad. mGAD67 or Ad. mPreproinsulin II-transfected NOD fibroblasts, however, these transplanted mice still showed insulitis as same degree as control mice. Th2 dominant pattern of cytokine expression was observed by RT-PCR method on the islets from NOD mice transplanted with GAD67 or proinsulin II-expressing fibrablasts. These results suggest that peripheral expression of GAD67 or proinsulin II in NOD mice could induce immunoregulatory Th2 cells that down-regulate diabetogenic Th1 cells. This experiment has implications for the application of the treatment for human type 1 diabetes.

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