| 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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| Co-Investigator(Kenkyū-buntansha) |
岩崎 師壽江 国立成育医療センター研究所, 共同研究管理室, 流動研究員
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥12,300,000 (Direct Cost: ¥12,300,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2004: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2003: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | Immunosuppressant / FTY720 / ICOS / Microchimerism / Quantitative RT-PCR / 抗ICOS抗体 / AdCTLA4-Ig / CD28ファミリー / 慢性拒絶反応 / 心臓移植 / 皮膚移植 / CD152 / sphingosine 1-phosphate receptors / 免疫学的メモリーT細胞 / 樹状細胞 / 遺伝子ベクター / 第三世代HIV改変lenti virusベクター / 移植免疫寛容 / CTLA-4Ig / メモリーT細胞 / 長期リンパ液排導 / TDL / 再循環 / 臓器移植 / 移植免疫 / 免疫寛容 |
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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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