Evidence that retinal pigment epithelium functions as an immune-privilegedtissue

PURPOSE. Tissues derived from immune-privileged sites sometimes possess spe cial 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 transp lanted 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 conjun ctival grafts as positive controls) were transplanted into the anterior cha mber, the subretinal space, the subconjunctival space, and underneath the k idney capsule of histoincompatible BALB/c mice. Transplant survival was eva luated by histology at selected time points after engraftment. Recipients w ere tested for acquisition of C57BL/6-specific delayed-type hypersensitivit y (DH) and for the ability to suppress DH. RESULTS. Allogeneic neonatal RPE grafts from normal donors showed significa ntly enhanced survival at all graft sites compared with conjunctival grafts . However, allogeneic RPE cell grafts from gld/gld mice were rapidly reject ed after transplantation beneath the kidney capsule. Allogeneic RPE grafts placed in extraocular sites induced systemic DH directed at donor alloantig ens, whereas RPE allografts placed intraocularly induced suppression of sys temic DH. CONCLUSIONS. Allogeneic neonatal RPE grafts, through constitutive expressio n of CD95 ligand, promote their own survival at heterotopic sites. Paradoxi cally, these grafts also display immunogenicity. Thus, neonatal RPE tissue owes its immune privilege to the capacity to prevent immune rejection rathe r than to inhibit sensitization.