Abstract
Significant advances derived from rodent models of penetrating keratoplasty have transformed our understanding of the pathogenesis of rejection of orthotopic corneal transplants. The high rate of success of corneal allografts placed in low-risk eyes without cover of immunosuppression arises from immune privilege of the cornea graft itself, and of the anterior chamber where it forms the anterior wall. Immune privilege owes its existence in penetrating keratoplasty to an absence of blood and lymph vessels in the graft and its bed, the absence of MHC class II+ antigen presenting cells in the graft, reduced expression of MHC-encoded alloantigens on graft cells, constitutive expression of T cell-deleting CD95 ligand on corneal graft endothelium, the existence of an immunosuppressive local microenvironment (aqueous humor), and the capacity of the graft to induce anterior chamber associated immune deviation (ACAID). The results of recent experiments provide answers to pertinent questions regarding cornea graft failure: How does the cornea as a graft suppress inflammation and angiogenesis locally? How does the graft promote ACAID to the alloantigens it expresses? and How do corneal cells reduce their vulnerability as targets of effector T cells? The answers offer the possibilities of novel strategies for preventing immune-based corneal allograft failure.
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Acknowledgements
I greatly appreciate the willingness of Drs Pedram Hamrah, M Reza Dana, Zdenka Haskova, Bruce Ksander, and Carolina Arancibia-Carcamo to permit me to present some of their important and seminal recent experimental findings.
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Streilein, J. New thoughts on the immunology of corneal transplantation. Eye 17, 943–948 (2003). https://doi.org/10.1038/sj.eye.6700615
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DOI: https://doi.org/10.1038/sj.eye.6700615
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