| Project/Area Number |
14207049
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General surgery
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| Research Institution | Keio University |
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Principal Investigator |
KITAJIMA Masaki Keio University, Department of Medicine, Professor, 医学部, 教授 (90112672)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMAZU Motohide Keio University, Department of Medicine, Assistant Professor, 医学部, 講師 (70124948)
WAKABAYASHI Go Keio University, Department of Medicine, Assistant Professor, 医学部, 講師 (50175064)
TANABE Minoru Keio University, Department of Medicine, Assistant Professor, 医学部, 講師 (50197513)
NIIMI Masanori Teikyo University, Department of Medicine, Associate Professor, 医学部, 助教授 (80198415)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥50,960,000 (Direct Cost: ¥39,200,000、Indirect Cost: ¥11,760,000)
Fiscal Year 2004: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2003: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2002: ¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
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| Keywords | regulatory cells / mucosal immunity / operational tolerance / adoptive transfer / cardiac grafts / regulatory dendritic cells / 抗原経口投与 / 抗原経気管支投与 / 生体臓器移植 / マウス心移植 / 気管内脾細胞投与 / CD4(+)CD25(+)細胞 / 臓器移植 / ドナー抗原気管内投与 / 生体肝移植 / CD4陽性CD25陽性T細胞 |
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| Research Abstract |
(1)Alloantigen or allopeptide can induce hyporesponsiveness to fully mismatched cardiac allografts when delivered intratracheally or orally.
(2)Alloantigen or allopeptide can generate regulatory cells when delivered intratracheally.
(3)The population of regulatory cells contains regulatory T cells and regulatory dendritic cells.
(4)The regulatory T cells and regulatory dendritic cells can suppress rejection of allogeneic heart grafts.
(5)The suppression by regulatory T cells and regulatory dendritic cells is donor specific.
(6)Intratracheal delivery of alloantigen combined with anti-CD4 mAb or anti-CD40L mAb induces operational tolerance to fully allogeneic cardiac allografts.
(7)CD80/86 pathway, signals of THF-family and PD-1 signal are necessary for induction of regulatory cells by intratracheal delivery of alloantigen, individually.
(8)IL-10 is essential for induction of regulatory cells by intratracheal delivery of alloantigen.
(9)Mycophenolate mofetil and Rapamycin work synergistically for induction of regulatory cells, although high dose of Tacrolimus, Azathioprine and Cyclosporine prevent generating regulatory cells.
(10)Histamine 2 receptor antagonist, serotonin receptor antagonist, ursodeoxycholic acid, MCI-186 (free radical scavenger) and anti-thrombin III can generate regulatory cells.
(11)The fraction of regulatory T cells is CD4^+CD25^+CTLA4^+ in our model.
(12)The number of CD4^+CD25^+CTLA4^+ cells decreased before rejection episode in preliminary clinical study.
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