| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
We have recently shown that (i) wt mice are tolerant, while TSHR KO mice are responsive to the mouse receptor in a mouse model of Graves’ disease using adenovirus expressing mouse TSHR, and (ii) anti-TSHR immune response could be adoptively transferred from TSHR KO to nude mice but that hyperthyroidism and TSAb were transient and soon changed to hypothyroidism and TBAb. Therefore, we here studied (i) the mechanisms of immune tolerance and response in wt KO mice, respectively, and (ii) those of immune response in the adoptive transfer model. In the evaluation of the peripheral tolerance, inhibition of co-inhibitory molecules and stimulation of co-stimulatory molecules increased the anti-TSHR antibodies, but did not develop TSAb or hyperthyroidism. On the other hand, the studies on central tolerance did not technically work well. In the adoptive transfer model, Graves’ disease could be maintained by repetitive immunization following transfer.
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