IMMUNITY AND IMMUNE PRIVILEGE ELICITED BY CULTURED RETINAL-PIGMENT EPITHELIAL-CELL TRANSPLANTS

Purpose. To determine whether cultured retinal pigment epithelial (RPE ) cells implanted in the subconjunctival space induce an immune respon se against autoantigens and whether an active downregulation is achiev ed by RPE grafts placed in the anterior chamber and within the subreti nal space. Methods. Cultured RPE cells from eyes of newborn C57BL/6 mi ce were implanted in the subconjunctival space, the anterior chamber, or the subretinal space of eves of adult C57BL/6 mice. At postimplanta tion day 12, the recipients were evaluated for RPE-specific delayed hy persensitivity and examined clinically and histologically for evidence of rejection. To facilitate their identification, RPE cells were labe led with 5-bromodeoxyuridine, before intraocular transplantation. Resu lts. Cultured RPE cells implanted in the subconjunctival space of syng eneic mice elicited an intense RPE-specific delayed hypersensitivity a ssociated with a vehement cellular infiltration of the graft when exam ined at postimplantation day 12. By contrast, grafts in the anterior c hamber and subretinal space displayed no evidence of rejection, and th eir recipients failed to display RPE-specific delayed hypersensitivity . Additionally, the spleens of these mice contained regulatory T cells that suppressed RPE-specific delayed hypersensitivity in naive syngen eic recipients. Conclusions. Cultured RPE cells can induce an immune r esponse against autoantigens. Implantation of RPE cells in immune-priv ileged sites of the eye induces a deviant immune response that is asso ciated with spleen cells that suppress RPE-specific delayed hypersensi tivity and autoimmune rejection.