2006 Fiscal Year Final Research Report Summary
Molecular mechanisms of immune privilege of corneal transplantation
| Project/Area Number |
17591857
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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 |
Ophthalmology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
HORI Junko Nippon Medical School, Faculty of Medicine, Associate Professor, 医学部, 助教授 (60251279)
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| Co-Investigator(Kenkyū-buntansha) |
KITAHARA Yuki Nippon Medical School, Faculty of Medicine, Research Associate, 医学部, 助手 (30360176)
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| Project Period (FY) |
2005 – 2006
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| Keywords | transplantation immunology / immune privilege / corneal transplantation / co-stimulation / reject ion / PD-1 / B7-H1 / apoptosis |
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| Research Abstract |
The programmed death-1 (PD-1) costimulatory pathway has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. We investigated the role of this pathway in establishing an immune privilege status of corneal allografts in mice. B7-H1, but not B7-DC or PD-1, was expressed constitutively in the eye, i.e., cornea, iris-ciliary body and retina. After corneal allografting, PD-1^+ CD4^+ T cells infiltrated and adhered with B7-H1^+ corneal endothelium. Blockade of PD-1 or B7-H1, but not B7-DC, led to accelerated corneal allograft rejection. In B7-H1-expressing corneal allografts, apoptosis of the infiltrating PD-1^+ CD4^+ or CD8^+ T cells was observed, after which there was allograft acceptance. In contrast, B7-H1 blockade suppressed apoptosis of infiltrating PD-1^+T cells, which led to allograft rejection. In vitro, destruction of corneal endothelial cells by alloreactive T cells was enhanced when the cornea was pre-treated with anti-B7-H1 antibody. This is the first demonstration that the constitutive expression of B7-H1 plays a critical role in corneal allograft survival. B7-H1 expressed on corneal endothelial cells maintains long-term acceptance of the corneal allografts by inducing apoptosis of effector T cells within the cornea.
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