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 response against autoantigens and whether an active downregulation is achieved by RPE grafts placed in the anterior chamber and within the subretinal space. Methods: Cultured RPE cells from eyes of newborn C57BL/6 mice were implanted in the subconjunctival space, the anterior chamber, or the subretinal space of eyes of adult C57BL/6 mice. At postimplantation day 12, the recipients were evaluated for RPE-specific delayed hypersensitivity and examined clinically and histologically for evidence of rejection. To facilitate their identification, RPE cells were labeled with 5-bromodeoxyuridine, before intraocular transplantation. Results: Cultured RPE cells implanted in the subconjunctival space of syngeneic mice elicited an intense RPE-specific delayed hypersensitivity associated with a vehement cellular infiltration of the graft when examined at postimplantation day 12. By contrast, grafts in the anterior chamber and subretinal space displayed no evidence of rejection, and their 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 syngeneic recipients. Conclusions: Cultured RPE cells can induce an immune response against autoantigens. Implantation of RPE cells in immune-privileged sites of the eye induces a deviant immune response that is associated with spleen cells that suppress RPE-specific delayed hypersensitivity and autoimmune rejection.