Immunological disruption of antiangiogenic signals by recruited allospecific T cells leads to corneal allograft rejection

Yaohong Tan, Fernando Cruz-Guilloty, Carlos A. Medina-Mendez, Nicholas J. Cutrufello, Rosa E. Martinez, Maitee Urbieta, David Wilson, Yiwen Li, Victor L Perez Quinones

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16 Citations (Scopus)

Abstract

Corneal transplantation is the most common solid organ transplantation. The immunologically privileged nature of the cornea results in high success rates. However, T cell-mediated rejection is the most common cause of corneal graft failure. Using antiangiogenesis treatment to prevent corneal neovascularization, which revokes immune privilege, prevents corneal allograft rejection. Endostatin is an antiangiogenic factor that maintains corneal avascularity. In this study, we directly test the role of antiangiogenic and immunological signals in corneal allograft survival, specifically the potential correlation of endostatin production and T cell recruitment. We report that 75% of the corneal allografts of BALB/c mice rejected after postoperative day (POD) 20, whereas all syngeneic grafts survived through POD60. This correlates with endogenous endostatin, which increased and remained high in syngeneic grafts but decreased after POD10 in allografts. Immunostaining demonstrated that early recruitment of allospecific T cells into allografts around POD10 correlated with decreased endostatin production. In Rag -/- mice, both allogeneic and syngeneic corneal grafts survived; endostatin remained high throughout. However, after T cell transfer, the allografts eventually rejected, and endostatin decreased. Furthermore, exogenous endostatin treatment delayed allograft rejection and promoted survival secondary to angiogenesis inhibition. Our results suggest that endostatin plays an important role in corneal allograft survival by inhibiting neovascularization and that early recruitment of allospecific T cells into the grafts promotes destruction of endostatin-producing cells, resulting in corneal neovascularization, massive infiltration of effector T cells, and ultimately graft rejection. Therefore, combined antiangiogenesis and immune suppression will be more effective in maintaining corneal allograft survival.

Original languageEnglish
Pages (from-to)5962-5969
Number of pages8
JournalJournal of Immunology
Volume188
Issue number12
DOIs
StatePublished - Jun 15 2012

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Endostatins
Allografts
T-Lymphocytes
Transplants
Corneal Neovascularization
Corneal Transplantation
Graft Rejection
Organ Transplantation
Cornea

ASJC Scopus subject areas

  • Immunology

Cite this

Tan, Y., Cruz-Guilloty, F., Medina-Mendez, C. A., Cutrufello, N. J., Martinez, R. E., Urbieta, M., ... Perez Quinones, V. L. (2012). Immunological disruption of antiangiogenic signals by recruited allospecific T cells leads to corneal allograft rejection. Journal of Immunology, 188(12), 5962-5969. https://doi.org/10.4049/jimmunol.1103216

Immunological disruption of antiangiogenic signals by recruited allospecific T cells leads to corneal allograft rejection. / Tan, Yaohong; Cruz-Guilloty, Fernando; Medina-Mendez, Carlos A.; Cutrufello, Nicholas J.; Martinez, Rosa E.; Urbieta, Maitee; Wilson, David; Li, Yiwen; Perez Quinones, Victor L.

In: Journal of Immunology, Vol. 188, No. 12, 15.06.2012, p. 5962-5969.

Research output: Contribution to journalArticle

Tan, Y, Cruz-Guilloty, F, Medina-Mendez, CA, Cutrufello, NJ, Martinez, RE, Urbieta, M, Wilson, D, Li, Y & Perez Quinones, VL 2012, 'Immunological disruption of antiangiogenic signals by recruited allospecific T cells leads to corneal allograft rejection', Journal of Immunology, vol. 188, no. 12, pp. 5962-5969. https://doi.org/10.4049/jimmunol.1103216
Tan Y, Cruz-Guilloty F, Medina-Mendez CA, Cutrufello NJ, Martinez RE, Urbieta M et al. Immunological disruption of antiangiogenic signals by recruited allospecific T cells leads to corneal allograft rejection. Journal of Immunology. 2012 Jun 15;188(12):5962-5969. https://doi.org/10.4049/jimmunol.1103216
Tan, Yaohong ; Cruz-Guilloty, Fernando ; Medina-Mendez, Carlos A. ; Cutrufello, Nicholas J. ; Martinez, Rosa E. ; Urbieta, Maitee ; Wilson, David ; Li, Yiwen ; Perez Quinones, Victor L. / Immunological disruption of antiangiogenic signals by recruited allospecific T cells leads to corneal allograft rejection. In: Journal of Immunology. 2012 ; Vol. 188, No. 12. pp. 5962-5969.
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