2005 Fiscal Year Final Research Report Summary
New immunosuppressive reagent FTY720 and its combined immunotherapy with anti-ICOS antibody to organ transplantation
| Project/Area Number |
14370368
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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 | National Research Institute for Child Health and Development |
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Principal Investigator |
KIMURA Hiromitsu National Research Institute for Child Health and Development, Division of Collaborative Research, The head of a laboratory (80115477)
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| Project Period (FY) |
2002 – 2005
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| Keywords | Immunosuppressant / FTY720 / ICOS / Microchimerism / Quantitative RT-PCR |
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| Research Abstract |
New immunosuppressive reagent FYY720, in particular, its effect on immunological memory was investigated. Employing sex-mismatched skin isograft model, FTY720 was found to be no serious effect on immunological memory despite of strong immunosuppressive activity.
As for co-stimulation molecule of CD28 superfamily, i.e., CTLA-4 and ICOS, was investigated in the preset study. Although single immunotherapy of Adenovirus vector encoding chimeric molecule of CTLA-4 and IgG (Ad-CTLA-4-IgG) and anti-ICOS monoclonal antibody had limited activity to rat cardiac allograft model. Thus cardiac allografts were ultimately rejected in chronic fashion under Ad-CfLA-4-IgG or anti-ICOS immunotherpy. In particular anti-ICOS single immunotherapy had less effective than CTLA4-IgG However, when the imuunotherapy of Ad-CTLA-4-IgG and anti-ICOS were combined, no rejection was observed. Moreover, immunohistological examination revealed that the combined Ad-CTLA-4-IgG and anti-ICOS immunotherapy were found to induce more complete tolerance than single immunotherapy. Nevertheless the combined immunotherapy failed to induce complete tolerance to skin allograft models. These results indicate that regulation of T cell activation co-stimulation molecules, in particular, CD28 superfamily, are apparent targets of imuunosuppression strategy.
In order to induce complete tolerance to skin allograft models, more precise study must be explored.
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[Journal Article] AdCTLA-4Ig combined with donor splenocytes, bone marrow cells and anti-ICOS antibody treatment induce tolerance in a rat heart transplantation model2004
Author(s)
Guo L, Fujino M, Kimura H, Funeshima N, Kitazawa Y, Harihara Y, Tezuka K, Makuuchi M, Suzuki S, LiXK.
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Journal Title
1Transplantation Internation Jan ; 17(1)
Pages: 15-21
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Simultaneous blockade of co-stimulatory signals, CD28 and ICOS, induced a stable tolerance in rat heart transplantati on2003
Author(s)
Guo L, Fujino M, Kimura H, Funeshima N, Kitazawa Y, Harihara Y, Tezuka K, Makuuchi M, Suzuki S, Li XK
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Journal Title
TranspIantImmunology 12
Pages: 41-48
Description
「研究成果報告書概要(和文)」より
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[Journal Article] SProlonged survival of rat hepatic allograft with mouse monoclonalantibody against inducible co-stimulator (ICOS)2002
Author(s)
Guo L, Xiao-Kang Li, Funeshima N, Fujino M, Nagata Y, Kimura H, Amemiya H, Enosawa S, Harihara, Y, Makuuchi M, Suzuki
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Journal Title
Transplantatio Apr 15 ; 73(7)
Pages: 1027-32
Description
「研究成果報告書概要(和文)」より
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[Journal Article] SProlonged survival of rat hepatic allograft with mouse monoclonal antibody against inducible co-stimulator (ICOS)2002
Author(s)
Guo L, Xiao-Kang Li, Funeshima N, Fujino M, Nagata Y, Kimura H. Amemiya H, Enosawa S, Harihara, Y, Makuuchi M, Suzuki
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Journal Title
Transplantation 73(7)
Pages: 1027-32
Description
「研究成果報告書概要(欧文)」より
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[Presentation] GENERATION OF GM-CSF INDEPENDENT MYELOID DENDRITIC CELLS(DC) FROM BONE MARROW CELLS (BMC) IN GM-CSF RECEPTOR DEFICIENT MOUSE2003
Author(s)
Eigo Satoh, Hua Yan, Robb L, Hajime Hikino, Tohko Miyagi, Hirohisa Saito, Daniel P. Gold, Xiao-K. Li, Kenichi Teramoto, Shigeki Arii, Hiromitsu Kimura
Organizer
8 th Congress of the Asian Society of Transplantation
Place of Presentation
Kuala Lumpur
Year and Date
20030923-20030927
Description
「研究成果報告書概要(欧文)」より
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[Presentation] CYTOKINE REQUIREMENT FOR THE GM-CSF INDEPENDENT DEVELOPMENT OF HUMAN DENDRITIC CELLS (DC) BY IN VITRO CULTURING OF HEMATOPOIETC STEM CELL.2003
Author(s)
Eigo Satoh, Xiao-K. Li, Yan Hua, Tohko Miyagi, Hirohisa Saito, Daniel P. Gold, Masayuki Fujino, Taga Tetsuya, Hiroshi Amemiya, Seiichi Suzuki, Kenichi Teramoto, Shigeki Arii, Hiromitsu Kimura
Organizer
8 th Congress of the Asian Society of Transplantation
Place of Presentation
Kuala Lumpur
Year and Date
20030923-20030927
Description
「研究成果報告書概要(欧文)」より
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