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 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / pharmacology
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Antigens, Surface / genetics
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Antigens, Surface / metabolism
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Apoptosis Regulatory Proteins / antagonists & inhibitors
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism
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Apoptosis*
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B7-1 Antigen / analysis
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B7-1 Antigen / metabolism*
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B7-H1 Antigen
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CD4-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / immunology
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Cornea / immunology*
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Cornea / metabolism
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Cornea / pathology
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Corneal Transplantation / immunology*
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Endothelial Cells / metabolism
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Graft Rejection / genetics
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Graft Rejection / immunology*
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Graft Rejection / pathology
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Graft Survival / drug effects
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Graft Survival / genetics
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Male
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / metabolism*
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Mice
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Mice, Inbred Strains
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Peptides / antagonists & inhibitors
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Peptides / metabolism*
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Programmed Cell Death 1 Ligand 2 Protein
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Programmed Cell Death 1 Receptor
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Transplantation, Homologous
Substances
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Antibodies, Monoclonal
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Antigens, Surface
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Apoptosis Regulatory Proteins
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B7-1 Antigen
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B7-H1 Antigen
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Cd274 protein, mouse
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Membrane Glycoproteins
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Pdcd1 protein, mouse
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Pdcd1lg2 protein, mouse
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Peptides
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Programmed Cell Death 1 Ligand 2 Protein
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Programmed Cell Death 1 Receptor