Subretinal space and vitreous cavity as immunologically privileged sites for retinal allografts.

PURPOSE

Because immune rejection is likely to be a major barrier to successful retinal transplantation, it is important to determine whether immune privilege for allogeneic retinal grafts is a feature of the subretinal space and vitreous cavity.

METHODS

Newborn neural retinas of C57BL/6 mice were implanted into the subretinal space, vitreous cavity, or subconjunctival space of eyes of adult BALB/c (disparate from C57BL/6 at major and minor histocompatibility loci). At postimplantation day 12, the recipients were evaluated for donor-specific delayed hypersensitivity and examined clinically and histologically for evidence of rejection.

RESULTS

Newborn neural retinal allografts in the subconjunctival space were destroyed by postimplantation day 12 and these recipients displayed intense donor-specific delayed hypersensitivity. By contrast, grafts in the subretinal space and vitreous cavity at postimplantation day 12 were found to be well differentiated and with no evidence of inflammation; these recipients failed to display donor-specific delayed hypersensitivity. Moreover, their spleens contained regulatory T cells that suppressed donor-specific delayed hypersensitivity in naive syngeneic recipients.

CONCLUSIONS

Allogeneic newborn neural retinal grafts implanted in the subretinal space and vitreous cavity experience immune privilege and induce deviant immune responses resembling anterior chamber associated immune deviation.