| Project/Area Number |
13671250
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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 |
General surgery
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| Research Institution | Jichi Medical School |
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Principal Investigator |
MIYAZAKI Kunihisa Dept.of Surgery, Jichi Medical School Assistant Prof., 医学部, 助手 (10260837)
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| Co-Investigator(Kenkyū-buntansha) |
LI Xiao-Kang 国立成育医療センター研究所, 移植・外科研究部, 室長 (60321890)
KONISHI Fumio Dept.of Surgery, Jichi Medical School Professor, 医学部, 教授 (20142242)
TOYAMA Nobuyuki Dept.of Surgery, Jichi Medical School Lecturer, 医学部, 講師 (10265283)
KIMURA Hiromitsu Dept.of Collab.Res., Natl.Inst.of Child Heal.& Deve.Director, 移植・外科研究部, 室長 (80115477)
森 康昭 自治医科大学, 医学部, 助手 (00254938)
足立 健介 自治医科大学, 医学部, 助手 (90285809)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | adenovirus / IDO / tryptophan / organ transplantation / cre / loxP / XS106 / gene therapy / dendritic cell / lentivirus vector / apoptosis / 膵頭移殖 / RCAS-1 / キヌレニン |
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| Research Abstract |
Purpose : Indoleamine 2,3-dioxygenase (IDO) is an enzyme, involved in the catabolism of tryptophan and has been show to prevent rejection of the fetus during pregnancy, probably by inhibiting alloreactive T cells. In the present study, we investigated whether DCs that are transfected with IDO cDNA in inhibition of T cell proliferation after antigen-specific interaction. Methods : IDO was expressed with a gene delivery system using a recombinantadenoviral vector and its expression and function were confirmed by Western blot, immunology staining and kynurenine assay. The expression of the surface molecular of the IDO-transfected XS106 DC clone (derived from A/J mice) was confirmed by FACS analysis. Alloreactive T cell proliferation was assayed after culture with IDO-expressed DC. Results : A recombinant adenoviral vector expressing IDO was successfully generated and its gene expression detected by Western blot and immune staining. Its catabolic effect was confirmed by increase the kynurenine concentration. It revealed that IDO-expressing XS106 DC were no changeable for CD86, CDllc and CD69 expression. After co-cultured IDO-expressing DC with B6 allogeneic splenic T cell, the proliferation of the T cell was inhibited significantly. Conclusions : These results suggest that over expression of the IDO in the DC was effective to inhibit T cell proliferation, and may expand a new immunomodulatory strategy to prevent the allo-rejection of the organ transplantation.
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