Purpose: Tissues derived from immune-privileged sites sometimes possess special characteristics that promote their own survival when transplanted to a nonprivileged site. This study was undertaken to evaluate whether retinal pigment epithelium (RPE) behaves as an immune-privileged tissue when transplanted extraocularly.
Methods: RPE grafts were prepared from eyes of neonatal C57BL/6 or C57BL/6 gld/gld (deficient in CD95 ligand expression) mice. These grafts (or conjunctival grafts as positive controls) were transplanted into the anterior chamber, the subretinal space, the subconjunctival space, and underneath the kidney capsule of histoincompatible BALB/c mice. Transplant survival was evaluated by histology at selected time points after engraftment. Recipients were tested for acquisition of C57BL/6-specific delayed-type hypersensitivity (DH) and for the ability to suppress DH.
Results: Allogeneic neonatal RPE grafts from normal donors showed significantly enhanced survival at all graft sites compared with conjunctival grafts. However, allogeneic RPE cell grafts from gld/gld mice were rapidly rejected after transplantation beneath the kidney capsule. Allogeneic RPE grafts placed in extraocular sites induced systemic DH directed at donor alloantigens, whereas RPE allografts placed intraocularly induced suppression of systemic DH.
Conclusions: Allogeneic neonatal RPE grafts, through constitutive expression of CD95 ligand, promote their own survival at heterotopic sites. Paradoxically, these grafts also display immunogenicity. Thus, neonatal RPE tissue owes its immune privilege to the capacity to prevent immune rejection rather than to inhibit sensitization.