Elucidation of the mechanism on carbohydrate antigen recognition by B cells through CD1d mediated signaling and establishment of a method to regulate B cells responding to the carbohydrate antigens in ABO-incompatible transplantation and xe
| Project/Area Number |
18390349
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Hiroshima University |
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Principal Investigator |
ASAHARA Toshimasa Hiroshima University, President (70175850)
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| Co-Investigator(Kenkyū-buntansha) |
OHDAN Hideki Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor (10363061)
伊禮 俊充 広島大学, 病院・医員 (20397946)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥17,520,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2007: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
Fiscal Year 2006: ¥7,900,000 (Direct Cost: ¥7,900,000)
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| Keywords | Transplant immunology / ABO-blood group incompatible transplantation Xenot / Antibody mediated rejection / NKT cell / CD1d / ABO不適合移植 / 抗体拒絶反応 |
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| Research Abstract |
In ABO-blood group incompatible transplantation and xenotransplantation, grafted organs will be rejected because antibody (Ab)-mediated rejection is induced in responses to blood group A/B antigens, Gal α 1-3Galb1-4GlcNAc (Gal) or N-glycolylneuraminic acid (NeuGc) carbohydrates, which are widely expressed on the organ vessel epithelia. We have attempted to establish a specific immunosuppressive method targeting B cells responding to A/B, Gal and NeuGc carbohydrate antigens.
In this study, we have analyzed the role of natural killer T (NKT) cells in the differentiation of B cells responding to the transplant-related carbohydrates. In the wild-type (WT) control mice, anti-A IgM/IgG Ab production occurred and was accelerated after the immunization with human red blood cells (RBCs) and α Galactosylceramide ( α GalCer) (an unique carbohydrate antigen that is presented on CD1d molecules and activates NKT cells). On the other hand, in the CD1d (ligand to the V α 14 T cell receptors used predominantly in NKT cells) knockout (KO) mice, anti-A IgM production was significantly reduced and anti-A IgG-class switching could not be observed. There was no difference in anti-allogeneic MHC Ab production between WT and CD1dKO mice, and IgG-class switching could be normally observed in both background mice. Based on these findings, it is likely that the suppressive modulation of CD1d molecule-mediated signaling between NKT cells and B cells might lead to the avoidance of Ab-mediated rejection in ABO-incompatible transplantation, whereas this strategy could not prevent Ab production from B cells responding to allogeneic MHC antigens. In order to investigate further such roles of NKT cells in the differentiation of B cells responding to the xenogeneic carbohydrate antigens, we have now established Gal/CD1d double KO mice and NeuGc/CD1d double KO mice by mating either Gal KO or NeuGc KO mice with CD1dKO mice.
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Report
(3 results)
Research Products
(72 results)
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[Journal Article] The persistent elimination of B cells responding to blood group A carbohydrates by synthetic group A carbohydrates and B-1 cell differentiation blockade : novel concept in preventing antibody-mediated rejection in ABO-incompatible transplantation2007
Author(s)
Toshimitsu, Irei, Hideki, Ohdan, Zhou, Wendy, Ishityama, Kohei, Yuka, Tanaka, Ide, Kentaro, Asahara, Toshimasa
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Journal Title
Blood 110(13)
Pages: 4567-75
Description
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[Journal Article] Role for CD47-SIRPalpha signaling in xenograft rejection by macrojthages2007
Author(s)
Ide, Kentaro, Hui, Wang, Tahara, Hiroyuki, Jianxiang, Liu, Xiaoying, Wang, Asahara, Toshimasa, Megan, Sykes, Yong-Guang, Yang, Ohdan, Hideki, Fuchimoto, Yasushi, Egawa, Hiroto, Asahara, Toshimasa
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Journal Title
Proc Natl Acad Sci USA 104(12)
Pages: 5062-6
Description
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[Journal Article] Evidence of immune tolerance to blood group antigens in a case of ABO-incompatible pediatric liver transplantation2007
Author(s)
Ohdan, Hideki, Zhou, Wendy, Tanaka, Yuka, Irei, Toshimitsu, Fuchimoto, Yasushi, Egawa, Hiroto, Asahara, Toshimasa
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Journal Title
Am J Transplant 7(9)
Pages: 2190-4
Description
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[Journal Article] Possible therapeutic effect of lipid supplementation on neurological complications in liver transplant recipients2007
Author(s)
Ide, Kentaro, Ohdan, Hideki, Tahara, Hirosyuki, Ishiyama, Kohei, Shishida, Masayuki, Irei, Toshimitsu, Ohira, Masahiro, Tashiro, Hirotaka, Itamoto, Toshiyuki, Asahara, Toshimasa
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Journal Title
Transpl Int 20(7)
Pages: 632-5
Description
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[Journal Article] Adoptive transfer of TRAIL-expressing natural killer cells prevents recurrence of hepatocellular carcinoma after partial hepatectomy2006
Author(s)
Ohira, Masahiro, Ohdan, Hideki, Mitsuta, Hiroshi, Ishiyama, Kohei, Tanaka, Yuka, Igarashi, Yuka, Asahara, Toshimasa
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Journal Title
Transplantation 82(12)
Pages: 1712-9
Description
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[Journal Article] Induction of endotoxin tolerance inhibits alloimmune responses2006
Author(s)
Ishiyama, Kohei, Ohdan, Hideki, Tokita, Daisuke, Shishida, Masayuki, Tanaka, Yuka, Irei, Toshimitsu, Asahara, Toshimasa
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Journal Title
Transpl Immunol 16(3-4)
Pages: 158-65
Description
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[Journal Article] Liver sinusoidal endothelial cells that endocytose allogeneic cells suppress T cells with indirect allospecificity2006
Author(s)
Tokita, Daisuke, Shishida, Masayuki, Ohdan, Hideki, Onoe, Takashi, Hara, Hidetaka, Tanaka, Yuka, Ishiyama, Kohei, Mitsuta, Hiroshi, Ide, Kentaro, Arihiro, Koji, Asahara, Toshimasa
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Journal Title
J Immunol 177(6)
Pages: 3615-24
Description
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[Journal Article] Near-infrared spectroscopic analysis of hemodynamics and mitochondrial redox in right lobe grafts in living-donor liver transplantation2006
Author(s)
Mitsuta, Hiroshi, Ohdan, Hideki, Fudaba, Yasuhiro, Irei, Toshimistu, Tashiro, Hirotaka, Itamoto, Toshiyuki, Asahara, Toshimasa
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Journal Title
Am J Transplant 6(4)
Pages: 797-805
Description
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[Presentation] Elucidation of the mehcanism of differentiation of B cells responding to blood group antigen and application to ABO-incompatible renal transplantation2008
Author(s)
T., Irei, H., Ohdan, Y., Igarashi, K., Ishiyama, Y., Tanaka, K., Ide, M., Shishida, M., Ohira, H., Tahara, M., Bansyodani, Y., Fudaba, F., Shintaku, T., Ishikawa, Y., Fukuda, T., Asahara
Organizer
The 41th Annual Meeting of Japan Clinical Renal Transplanataion Society
Place of Presentation
Hamamatsu
Description
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[Presentation] Elucidation of the mehcanism of differentiation of B cells responding to blood group antigen (co-stimulating effect from NKT cells) and application to ABO-incompatible organ transplantation2007
Author(s)
T., Irei, H., Ohdan, K., Ishiyama, Y., Tanaka, K., Ide, M., Shishida, M., Ohira, Y., Igarashi, H., Tahara, B., Nabin, T., Asahara
Organizer
The 43th Annual Meeting of Japan Society for Transplantation
Place of Presentation
Sendai
Year and Date
2007-11-24
Description
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[Presentation] Antibody-dependent rejection against xenogeneic antigen N-glycolylneuraminic acid (NeuGc)2007
Author(s)
H., Tahara, H., Ohdan, K., Ide, N., Basnet, K., Ishiyama, M., Shishida, Y., Tanaka, T., Irei, M., Ohira, Y., Igarashi, K., Kajitani, M., Banshodani, H., Takematsu, Y., Kozutsumi, T., Asahara
Organizer
The 43th Annual Meeting of Japan Society for Transplantation
Place of Presentation
Sendai
Year and Date
2007-11-24
Description
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[Presentation] Possibility of B cell immunotorelance induction by liver sinusoidal endothelial cells2007
Author(s)
Y., Igarashi, H., Ohdan, T., Irei, M., shishida, Y., Tanaka, T., Asahara
Organizer
The 43th Annual Meeting of Japan Society for Transplantation
Place of Presentation
Sendai
Year and Date
2007-11-24
Description
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[Presentation] A case of ABO-incompatible liver transplantationby using the immunosuppressive regimenl without splenectomy based on the B cell developmental theory responding to blood group carbohydrates2007
Author(s)
T., Irei, H., Ohdan, Y., Igarashi, K., Ishiyama, S., Kuroda, Y., Tanaka, K., Ide, M., Shishida, M., Ohira, H., Tahara, M., Bansyodani, N., Basnet, M., doskari,T., Asahara
Organizer
The 25th Annual Meeting of Chugoku Shikoku Clinical Organ Transplantation society
Place of Presentation
Shimane
Year and Date
2007-08-18
Description
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[Presentation] Each cases of ABO-incompatible liver and kidney transplantation using the immunosuppressive regimenl without splenectomy based on the B cell developmental theory responding to blood group carbohydrates2007
Author(s)
T., Irei, H., Ohdan, Y., Igarashi, K., Ishiyama, M., Bansyodani, Y., Tanaka, K., Ide, M., Shishida, M., Ohira, H., Tashiro, T., Itamoto, T., Asahara
Organizer
The l4th Annual Meeting of ABO-incompatible Transplantation Society
Place of Presentation
Nagoya
Year and Date
2007-08-05
Description
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[Presentation] Immunogenicity of N-Glycolylneuraminic Acid(NeuGc) in Xenotransplantation2007
Author(s)
H., Tahara, H., Ohdan, K., Ide, N.B., Basnet, T., Asahara, H., Takematsu, Y., Kozutsumi
Organizer
American Transplant Congress 2007
Place of Presentation
San Francisco,USA
Year and Date
2007-05-06
Description
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[Presentation] B-Cell Tolerance to Blood-Group Antigens Post Pediatric ABO-Incompatible Liver Transplantation2007
Author(s)
Y., Igarashi, H., Ohdan, Y., Tanaka, M., Shishida, T., Irei, T., Asahara
Organizer
American Transplant Congress 2007
Place of Presentation
San Francisco,USA
Year and Date
2007-05-06
Description
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[Presentation] Mechanism of avoidance of xenogeneic rejection by macrophages through intracellular inhibitory CD47-SIRPa signaling2007
Author(s)
K., Ide, H., Ohdan, H., Tahara, N., Basnet, K., Ishiyama, Y., Tanaka, M., Shishida, T., Irei, M., Ohira, Y., Igarashi, T., Asahara
Organizer
The 10th Meeting of Japanese Xenotransplantaion Society
Place of Presentation
Tokyo
Year and Date
2007-03-10
Description
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[Presentation] Immunogenicity of xenogeneic antigen N-glycolylneuraminic acid (NeuGc)2007
Author(s)
H., Tahara, H., Ohdan, K., Ide, N., Basnet, K., Ishiyama, M., Shishida, Y., Tanaka, T., Irei, M., Ohira, Y., Igarashi, M., Doskali, H., Takematsu, Y., Kozutsumi, T., Asahara
Organizer
The 10th Meeting of Japanese Xenotransplantaion Society
Place of Presentation
Tokyo
Year and Date
2007-03-10
Description
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[Presentation] B cell tolerance to blood-group antigens post pediatric ABO-incompatible liver transplantation2007
Author(s)
Y., Igarashi, H., Ohdan, T., Irei, M., Shishida, Y., Tanaka, T., Asahara
Organizer
13th Congress of the European Society for Transplantation
Place of Presentation
Prague,Czech
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[Presentation] Role of antibodies against N-glycolylneuraminic acid (NeuGc) in acute vascular rejection caused by anti-non-Gal antibodies2007
Author(s)
H., Tahara, H., Ohdan, K., Ide, Basnet, NB., H., Takematsu, Y., Kozutsumi, T., Asahara
Organizer
CTS-IPITA-IXA2007 Joint Conference
Place of Presentation
Mineapolice, USA
Description
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[Presentation] Genetic induction of human CD47 on porcine cells prevents macrophagemediated xenograft rejection through inhibitory signaling to SIRPα2007
Author(s)
K., Ide, H., Wang, H., Tahara, T., Asahara, Sykes, M., Yang YG., H., Ohdan
Organizer
CTS-IPITA-IXA2007 Joint Conference
Place of Presentation
Mineapolice, USA
Description
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[Presentation] Human CD47 expression protects porcine cells from xenogeneic human macrophage phagocytosis through inhibitory CD47-SIRPa signaling (Young Investigator Award)2007
Author(s)
K., Ide, H., Wang, T., Asahara, M., Sykes, Y.G., Yang, H., Ohdan
Organizer
The First Joint International Transpl ant Meeting / The Transplantation Society(TTS) / WTC2006
Place of Presentation
Boston, USA
Description
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[Presentation] Therapeutic strategy for ABO-incompatible liver transplantation based on the B cell developmental theory responding to blood group carbohydrates2007
Author(s)
T., Irei, H., Ohdan, K., Ishiyama, Y., Tanaka, K., Ide, M., Shishida, M., Ohira, Y., Igarashi, H., Tahara, B., Nabin, M., Doskari, T., Asahara
Organizer
The 25th annual meeting of Japanese Liver Transplantaion Society
Place of Presentation
Tokyo
Description
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[Presentation] Application of Immunosuppressive strategy for ABO-incompatible renal transplantation based on the B cell developmental theory responding to blood group carbohydrates.2007
Author(s)
T., Irei, H., Ohdan, Y., Igarashi, K., Ishiyama, Y., Tanaka, K., Ide, M., Shishida, M., Ohira, H., Tahara, M., Bansyodani, T., Asahara
Organizer
The 40th Annual Meeting of Janan Clinical renal Transplanataion Society
Place of Presentation
Kanazawa
Description
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[Presentation] Avoidance of xenogeneic rejection by macrophages through intracellular inhibitory CD47-SIRPa signaling2006
Author(s)
K., Ide, H., Ohdan, H., Tahara, K., Ishiyama, Y., Tanaka, M., Shishida, T., Irei, M., Ohira, T., Asahara
Organizer
The 42th Annual Meeting of Japan Society, for Transplantation
Place of Presentation
Chiba
Year and Date
2006-09-08
Description
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[Presentation] The elucidation of B cell deveropmental mechanism responding to T cell independent blood group carbohydrates and the establishment of immunosippressive methodology for such Bcells2006
Author(s)
T., Irei, H., Ohdan, K., Ishiyama, H., Mitsuta, Y., Tanaka, K., Ide, M., Shishida, M., Ohira, T., Asahara
Organizer
The 42th Annual Meeting of Japan Society, for Transplantation
Place of Presentation
Chiba
Year and Date
2006-09-08
Description
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[Presentation] The new methodology of the persistent elimination of B cells responding to blood group carbohydrates using the immunotoxin and the possibility of application to ABO incompatible organ transplantation2006
Author(s)
T., Irei, H., Ohdan, W., Zhou, K., Ishiyama, Y., Tanaka, K., Ide, M., Shishida, M., Ohira, Y., igarashi, H., Tahara, T., Asahara
Organizer
The l3th Annual Meeting of ABO-incompatible Transplantation Society
Place of Presentation
Nagoya
Year and Date
2006-08-06
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