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B7-H1-Induced Apoptosis as a Mechanism of Immune Privilege of Corneal Allografts
Open accessAbstract
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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“An active local or peripheral tolerance to prevent runaway immune responses can be induced in some cases through the conversion of T cell to regulatory T cells (Treg) or the apoptosis of infiltrated effector T cells by inhibitory molecules expressed on the retinal pigmented epithelium (RPE) or resident stromal cells [9][10][11].”
From Risk mitigation of immunogenicity: a key to personalized retinal gene therapy (2021) · cites this paper as [11]
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Metadata
- Authors
- Hori, J., Wang, M., Miyashita, M., Tanemoto, K., Takahashi, H., Takemori, T., Okumura, K., Yagita, H., & Azuma, M.
- Affiliations
- Nippon Medical School (JP)
- National Institute of Infectious Diseases (JP)
- Juntendo University (JP)
- Department of Immunology, Juntendo University School of Medicine , Tokyo ,
- Tokyo Medical and Dental University (JP)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-11-01
- Volume
- 177
- Issue
- 9
- Pages
- 5928-5935
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W2150372796
- Cited by
- 208
- References
- 58
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 11 · 2020: 16 · 2019: 8 · 2018: 10 · 2017: 8 · 2016: 12 · 2015: 10 · 2014: 7 · 2013: 18 · 2012: 7
- FWCI
- 5.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Ophthalmology › Corneal surgery and disorders
- Health Sciences › Medicine › Surgery › Transplantation: Methods and Outcomes
- Keywords
- PD-L1, PD-1, immune privilege, corneal allograft, corneal endothelium, T cell apoptosis, allograft rejection, costimulatory molecules, PD-L2, CD4+ T cells, CD8+ T cells
- MeSH terms
- Animals, Antibodies, Monoclonal, Antigens, Surface, Cornea, Graft Rejection, Graft Survival, Male, Membrane Glycoproteins, Mice, Inbred Strains, Peptides, Transplantation, Homologous, CD4-Positive T-Lymphocytes, Corneal Transplantation, Apoptosis, B7-1 Antigen, CD8-Positive T-Lymphocytes, Endothelial Cells, Apoptosis Regulatory Proteins, Mice, B7-H1 Antigen, Programmed Cell Death 1 Receptor, Programmed Cell Death 1 Ligand 2 Protein
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