Unconventional rejection of neural retinal allografts implanted into the immunologically privileged site of the eye

The unique feature of neural transplantation in the central nervous system is that the graft is derived from and implanted into an immunologically privileged site. The eye, as a part of the central nervous system, normally maintains an immunosuppressive microenvironment in which alloantigens induce an active down-regulation of specific delayed hypersensitivity. To determine whether neural retinal allografts are eventually rejected and, if so, what type of immunity is associated with rejection, we implanted allogeneic and syngeneic newborn neural retinal grafts into the anterior chamber of the eyes of immune-competent mice. In addition, similar allografts were implanted into severe combined immune-deficient (SCID) mice. The fate of these grafts was determined by clinical and histological examination. At post-implantation day 12, all allogeneic and syngeneic grafts survived comparably well with no evidence of inflammation. At post-implantation day 35, the syngeneic grafts in the immune-competent mice and the allogeneic grafts in the SCID mice continued to thrive, whereas the allografts in the immune-competent mice were remarkably reduced in size and had lost the organization of their retinal cell layers. Interestingly, these grafts' deterioration occurred with no obvious cellular infiltration. When systemic graft-specific immunity was examined, it was found that delayed hypersensitivity was impaired at post-implantation day 12 in allograft recipients. However, by post-implantation 35 day when deterioration was detected in these grafts, suppression of immunity was replaced by vigorous delayed hypersensitivity. These results suggest that intraocular retinal allografts eventually succumb to rejection and that rejection is correlated with the emergence of donor-specific delayed hypersensitivity. The possible relationships of atypical, chronic rejection of intraocular neural retinal allografts to emergent delayed hypersensitivity are discussed.