Abstract: Keratoplasty is the oldest and one of the most successful forms of solid tissue transplantation. In the United States, over 33,000 corneal transplants are performed each year. Unlike other forms of tissue transplantation, keratoplasties are routinely performed without the aid of tissue typing or systemic immunosuppressive drugs. In spite of this, 90 % of the first-time corneal transplants will succeed–a condition that demonstrates the immune privilege of keratoplasties. The avascular nature of the corneal allograft bed led many to suspect that corneal grafts were sequestered from the immune apparatus. Although pleasing in its simplicity, this explanation has given way to a more comprehensive hypothesis that embodies multiple, interdependent mechanisms, which promote the long-term survival of corneal allografts. These mechanisms conspire to interrupt the transmission of immunogenic stimuli to peripheral lymphoid tissues; induce the generation of a deviated immune response; and neutralize immune effector elements at the hostgraft interface. This paradigm is analogous to a three-legged stool. Disassembly of any one of the three components results in the collapse of immune privilege. Strategies to re-establish corneal immune privilege may have clinical application for high-risk hosts who have rejected previous corneal allografts. J. Leukoc. Biol. 74: 000–000; 2003
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