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* Department of Ophthalmology, Nippon Medical School, Tokyo, Japan;
Department of Immunology, National Institute of Infectious Disease, Tokyo, Japan;
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan; and
Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
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 pretreated with anti-B7-H1 Ab. 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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1 This study was supported in part by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (to J.H.).
2 Address correspondence and reprint requests to Dr. Junko Hori, Department of Ophthalmology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo, Tokyo, 113-8602, Japan. E-mail address: jhori-tky{at}umin.ac.jp
3 Abbreviations used in this paper: ACAID, anterior chamber-associated immune deviation; PD-1, programmed death-1; DC, dendritic cell; DAPI, 4',6'-diamidino-2-phenylindole; AC, anterior chamber; PI, propidium iodide; DH, delayed hypersensitivity.
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