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Corneal transplantation is the oldest, most common, and arguably, the most successful form of tissue transplantation. In the United States alone, over 40,000 corneal transplantations are performed each year. Less than 10% of the uncomplicated, first-time corneal grafts will undergo immune rejection even though HLA matching is not routinely performed and the use of immunosuppressive drugs is limited to the topical application of corticosteroids. The success of corneal transplantations predates the use of corticosteroids and further emphasizes the remarkable privilege of corneal allografts.Several laboratories have used rat and mouse models of orthotopic corneal transplantation (keratoplasty) in an attempt to understand the basis for the immune privilege of corneal allografts.The time-honored explanation for the immune privilege of corneal allografts was based on the conspicuous avascularity of the cornea, which was believed to sequester the graft from the immune apparatus. However, results from several laboratories indicate that at least three additional features of the corneal graft contribute to its immune privileged status: (a) absence of donor-derived, antigen-presenting passenger Langerhans cells in the corneal graft; (b) expression of Fas ligand on the epithelium and endothelium of the corneal allograft; and (c) capacity of the corneal allograft to induce immune deviation of the systemic immune response.The immune privilege of corneal allografts is a product of at least three unique qualities of the corneal allograft that conspire to interfere with the induction and expression of allodestructive immune responses.