B7-H1-induced apoptosis as a mechanism of immune privilege of corneal allografts.
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.
Hori
Junko
J
Department of Ophthalmology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo, Tokyo 113-8602, Japan. jhori-tky@umin.ac.jp
Wang
Mingcong
M
Miyashita
Megumi
M
Tanemoto
Keiko
K
Takahashi
Hiroshi
H
Takemori
Toshitada
T
Okumura
Ko
K
Yagita
Hideo
H
Azuma
Miyuki
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018122:B7-1 Antigen / Q000032:analysis / Q000378:metabolism*; D060890:B7-H1 Antigen; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003315:Cornea / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016039:Corneal Transplantation / Q000276:immunology*; D042783:Endothelial Cells / Q000378:metabolism; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; C491383:Pdcd1 protein, mouse; C556978:Pdcd1lg2 protein, mouse; D010455:Peptides; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor