2002 Fiscal Year Final Research Report Summary
THE APPLICATION OF THE DENDRITIC CELL GENE THERAPY IN TRANSPLANTATION FIELD -Induction of antigen-specific T cell proliferation by Indoleamine 2,3-dioxygenase cDNA-transfected dendritic cells-
| 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) |
李 小康 国立成育医療センター研究所, 移植・外科研究部, 室長
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)
LI Xiao-Kang Dept.of Innov.Surg., Natl.Inst.of Child Heal.& Deve.Lab head (60321890)
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| Project Period (FY) |
2001 – 2002
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| Keywords | adenovirus / IDO / tryptophan / organ transplantation / cre / loxP / XS106 / gene therapy / dendritic cell |
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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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Research Products
(18 results)
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[Publications] X-K.Li, M.Fujino, A.Sugioka, M.Morita, T.Okuyama, L.Guo, N.Funeshima, H.Kimura, S.Enosawa, H.Amemiya, and S.Suzuki: "Fulminant Hepatitis by Fas-Ligand Expression in MRL-lpr/lpr Mice Grafted with Fas-Positive Livers and Wild-Type Mice with Fas-Mutant Livers"Transplantation. 71(4). 503-508 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] M.Fujino, X-K.Li, T.Suda, M.Hashimoto, K.Okabe, H.Yaginuma, K.Mikoshiba, L.Guo, T.Okuyama, S.Enosawa, H.Amemiya, T.Amano and S.Suzuki: "In vitro prevention of cell-mediated xenograft rejection via the Fas/FasL-pathway in CrmA-transducted porcine kidney cells"Xenotransplantation. 8(2). 115-124 (2001)
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[Publications] X-K.Li, M.Kosuga, K.Tokieda, A.Kanaji, Y.Fukuhara, M.Hashimoto, K.Okabe, H.Yaginuma, M.Yamada, S.Suzuki, T,Okuyama: "Prolongation of transgene by co-expression of cytokine response modifier A in rodent liver after adenoviral gene transfer"Mol Ther. 5. 262-268 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] L Guo, X-K.Li, N.Funeshima, M.Fujino, Y.Nagata, H.Kimura, H.Amemiya, S.Enosawa, T.Tsuji, Y.Harihara, M.Makuuchi, S.Suzuki: "Prolonged survival in rat liver transplantation woth mouse monoclonal antibody against aninducible co-stimulator (ICOS)"Transplantation. 73(7). 1027-1032 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] M.Fujino, M.Kawasaki, N,Funeshima, Y.Kitazawa, M.Kosuga, K.Okabe, M.Hashimoto, H.Yaginuma, K.Mikoshiba, T.Okuyama, S.Suzuki, X-K.Li: "CrmA gene expression protects mice against concanavalin-A induced hepatitis by inhibiting IL-18 secretion and hepatocyte apoptosis"Gene Ther. (In press).
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「研究成果報告書概要(欧文)」より
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[Publications] M.Fujino, K.Adachi, M.Kawasaki, Y.Kitazawa, N,Funeshima, T.Okuyama, H.Kimura, S,Suzuki, X-K.Li: "Selective Prolonged Survival of Rat Liver Allograft with Adenoviral Gene Transfection of Human Immunodeficiency Virus Type 1 (HIV-1) nef"Liver Transplant. (In press).
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[Publications] Y.Fukuhara, A.Hirasawa, X-K.Li, M.Kawasaki, M.Fujino, N.Funeshima, S.Katsuma, S.Shiojima, M.Yamada, T.Okuyarm, S.Suzuki, G.Tsujimoto: "Gene Expression Profile in the Regenerating Rat Liver after Partial Hepatectomy"J Hepatol. (In press).
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「研究成果報告書概要(欧文)」より
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[Publications] L Guo, M.Fujino, H.Kimura, N.Funeshima, Y.Kitazawa, Y.Harihara, K.Tezuka, M.Makuuchi, S.Suzuki, X-K.Li: "Simultaneous Blockade of Co-stimulatory Signals, CD28 and ICOS, Induced a Stable Tolerance in Rat Heart Transplantation"Transpl Immunol. (In press).
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「研究成果報告書概要(欧文)」より
