Immune responses elicited by transplantation and tissue-restricted antigens expressed on retinal tissues implanted subconjunctivally

Abstract

In recent years there has been renewed interest in experimental retinal transplantation. Immunological rejections represent a major barrier to the success of retinal transplants. We recently reported that strongly histoincompatible neuroretinal grafts placed in the subconjunctival space of adult recipient mice were rejected, whereas similar grafts placed in the anterior chamber of the eye were accepted. Since retinal tissues are known to express retina-restricted autoantigens that can induce specific systemic immune responses and can serve as targets of destructive autoimmune attack, it is important to determine whether retinal transplants can evoke immune responses directed at retina-restricted antigens, and whether such responses might be deleterious to the graft. In this study, neonatal neural retinal grafts were placed into the subconjunctival space of eyes of normal allogeneic and syngeneic mice. Delayed hypersensitivity to the relevant alloantigens and to putative retina-restricted autoantigens was assayed. The results reveal that neural retina grafts sensitized their recipients to both alloantigens and retina-specific autoantigens. Moreover, in some recipients, a delayed, destructive uveitis developed, implying that graft-elicited immune responses directed at retina-restricted antigens may provoke autoimmune reactions in previously normal eyes of recipients. These findings indicate that grafts of developing neural retina tissue express both transplantation antigens and retina-restricted antigens in immunogenic form, and that grafting leads to systemic immunization against both sets of antigens.