| Project/Area Number |
21591333
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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 |
Pediatrics
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
ETO Yoshikatsu 東京慈恵会医科大学, 医学部, 教授 (50056909)
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| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Hiroshi 東京慈恵会医科大学, 医学部, 講師 (90266619)
KOBAYASHI Masahisa 東京慈恵会医科大学, 医学部, 講師 (20312019)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ライソゾーム蓄積症 / ポンぺ病 / 酵素補充療法 / 抗体 / 抗CD3抗体 / ポンペ病 / アナフィラキシー / ライソゾーム病 / 免疫応答 / 免疫寛容 / 制御性T細胞 |
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| Research Abstract |
Animal and human studies of enzyme replacement therapy for Pompe disease have indicated that antibodies(Abs) generated against infused recombinant humanα-glucosidase can have a negative impact on the therapeutic outcome and cause hypersensitivity reactions. We showed that parenteral administration of anti-CD3 Abs into mice can reduce the titer of anti-humanα-glucosidase Abs in wild-type mice administered the enzyme. Mice that had been treated with anti-CD3 Abs and then subjected to a secondary challenge withα-glucosidase showed a lower increase in Ab titers than control mice. Moreover, the administration of anti-CD3 Abs also reduced the levels of pre-existing Abs. Treatment with anti-CD3 Abs also prevented a lethal hypersensitivity reaction and reduced the Ab titers in a mouse model of Pompe disease. Mice treated with anti-CD3 Abs showed reduced numbers of CD4^+and CD8^+cells, and an increased ratio of CD4^+CD25^+/CD4^+and CD4^+CD25^+FoxP3^+/CD4^+cells. When the CD4^+CD25^+cells were depleted using anti-CD25 Abs, the observed reduction in Abs against the enzyme by anti-CD3 Abs was abrogated. This suggests that CD4^+CD25^+cells are important for the immune suppressive activity of anti-CD3 Abs. In summary, anti-CD3 Abs are useful for inducing immune tolerance to enzyme replacement therapy for Pompe disease.
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