Molecular mechanisms of immunity in corneal allotransplantation and xenotransplantation

Abstract

Corneal allotransplantation is the most common and successful form of solid organ transplantation in humans. In uncomplicated cases, the two-year graft survival rate is over 90%. This extraordinary success can be attributed in part to various features of the normal cornea and anterior segment that together account for their ‘immune-privileged’ status. However, despite this success, a significant number of corneal grafts fail and immunological rejection remains by far the leading cause of graft failure. Studies on animal models of corneal transplantation have yielded a wealth of information on the molecular and cellular features of graft rejection, and have established that this process is mediated primarily by CD4⁺ T cells of the T helper 1 (Th1) phenotype. In addition, studies have elucidated that certain facets of allosensitisation differ between corneal and other solid organ transplants. On the basis of these findings, novel experimental strategies selectively targeting the afferent or efferent arms of corneal alloimmunity have provided promising results in preventing corneal allograft rejection in the laboratory. Finally, because of the global shortage of human donor corneas, there is currently renewed interest in the possibility of using corneas from other species for transplantation into human eyes (xenotransplantation). Preliminary studies on animal models of corneal xenotransplantation have documented both antibody-mediated and cell-mediated responses that might play important roles in the accelerated rejection observed in corneal xenotransplants. This review synthesises the principal concepts emerging from studies of the molecular mechanisms in corneal transplant immunology.