| Project/Area Number |
16591248
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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 | The University of Tokyo |
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Principal Investigator |
BECK Yoshifumi The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (70199454)
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| Co-Investigator(Kenkyū-buntansha) |
TAHARA Hideaki The University of Tokyo, Institute of medical science, Professor, 医科学研究所, 教授 (70322071)
TAKAYAMA Takuya The University of Tokyo, Instituteof medical science, research associate, 医科学研究所, 助手 (10332579)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | HLA / regulatory T cell / CD4+CD25+ / peptide / transgenic mouse / thymus / 移植 / 免疫寛容 / HLA / CD4+CD25+T細胞 / マウス / 心移植 / 移植免疫 / CD4CD25 / 制御性T cell / FoxP3 |
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| Research Abstract |
CD4+CD25+ regulatory T cells are selected in the thymus to control autoreactive thymic escapees preventing autoimmunity that can not be achieved by negative selection or deletion alone, thus playing an important role in the maintenance of immunological homeostasis. Not only significant in preventing autoimmunity, CD4+CD25+ regulatory T cells have also been shown to be involved in allograft tolerance in organ transplantation. Recent studies suggest that Foxp3, which encodes Scurfin, a member of the forkhead family of transcriptional regulators, is the key regulatory gene for the development of CD4+CD25+ regulatory T cells. We have formerly introduced two lines of HLA class I transgenic mice valuable to elucidate the role of HLA class I molecules in transplantation biology. Here, using a heterotopic cardiac transplantation model, we show that intrathymic inoculation of donor HLA class I derived synthetic peptide results in elevation of Foxp3 level in graft infiltrating lymphocytes and acceptance of the vascularized allograft. In addition, we demonstrate by adoptive transfer experiments that CD4+CD25+ regulatory T cells obtained following intrathymic inoculation of the synthetic peptide effectively induce graft specific tolerance without preconditioning of the recipient or use of additional immunosuppressive drugs. The study provides evidence suggestive of novel therapeutic option with CD4+CD25+ applicable to clinical transplantation.
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