HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hori, J. Articles by Azuma, M. Search for Related Content PubMed PubMed Citation Articles by Hori, J. Articles by Azuma, M.

B7-H1-Induced Apoptosis as a Mechanism of Immune Privilege of Corneal Allografts¹

Junko Hori^2,*, Mingcong Wang^*, Megumi Miyashita^*, Keiko Tanemoto^*, Hiroshi Takahashi^*, Toshitada Takemori, Ko Okumura, Hideo Yagita and Miyuki Azuma

^* 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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.

This article has been cited by other articles:

				S. Calbo, H. Delagreverie, C. Arnoult, F.-J. Authier, F. Tron, and O. Boyer Functional Tolerance of CD8+ T Cells Induced by Muscle-Specific Antigen Expression J. Immunol., July 1, 2008; 181(1): 408 - 417. [Abstract] [Full Text] [PDF]

				M. Lafon, F. Megret, S. G. Meuth, O. Simon, M. L. Velandia Romero, M. Lafage, L. Chen, L. Alexopoulou, R. A. Flavell, C. Prehaud, et al. Detrimental Contribution of the Immuno-Inhibitor B7-H1 to Rabies Virus Encephalitis J. Immunol., June 1, 2008; 180(11): 7506 - 7515. [Abstract] [Full Text] [PDF]

				K. L. Alderson, Q. Zhou, V. Berner, D. E. C. Wilkins, J. M. Weiss, B. R. Blazar, L. A. Welniak, R. H. Wiltrout, D. Redelman, and W. J. Murphy Regulatory and Conventional CD4+ T Cells Show Differential Effects Correlating with PD-1 and B7-H1 Expression after Immunotherapy J. Immunol., March 1, 2008; 180(5): 2981 - 2988. [Abstract] [Full Text] [PDF]

				V. Dal Secco, A. Riccioli, F. Padula, E. Ziparo, and A. Filippini Mouse Sertoli Cells Display Phenotypical and Functional Traits of Antigen-Presenting Cells in Response to Interferon Gamma Biol Reprod, February 1, 2008; 78(2): 234 - 242. [Abstract] [Full Text] [PDF]

				L. Shen, Y. Jin, G. J. Freeman, A. H. Sharpe, and M. R. Dana The Function of Donor versus Recipient Programmed Death-Ligand 1 in Corneal Allograft Survival J. Immunol., September 15, 2007; 179(6): 3672 - 3679. [Abstract] [Full Text] [PDF]

				C. Petrovas, D. A. Price, J. Mattapallil, D. R. Ambrozak, C. Geldmacher, V. Cecchinato, M. Vaccari, E. Tryniszewska, E. Gostick, M. Roederer, et al. SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection Blood, August 1, 2007; 110(3): 928 - 936. [Abstract] [Full Text] [PDF]