Impaired cell-mediated immunity in mice bearing healthy orthotopic corneal allografts

A very high proportion of orthotopically grafted, histoincompatible corneas are accepted in healthy condition for prolonged intervals (> 8 weeks) by naive untreated BALB/c mice. Because these grafts form the anterior surface of the anterior chamber of the eye and because alloantigens placed in the anterior chamber elicit a deviant, stereotypic, systemic immune response known as anterior chamber-associated immune deviation, we have examined the state of alloantigen-specific cell-mediated immunity in BALB/c mice with accepted corneal allografts, as well as mice that had rejected their corneal grafts. Attempts to induce alloantigen-specific delayed hypersensitivity (DH) by s.c. injections of lymphoid cells, genetically identical to the grafts, resulted in positive responses only in "rejector" mice; "acceptor" mice failed to develop or display DH. Spleens cells from acceptors and rejectors were then assayed for the ability to suppress local adoptive transfer of alloantigen-specific DH. It was found that transfer reactions failed to develop if spleen cells from acceptor mice were added to the inoculum, whereas spleen cells from rejected mice had no similar inhibitory effects. The suppression mediated by acceptor spleen cells in local adoptive transfer assays was determined to be specific for the alloantigens expressed on the long-standing corneal allografts. We conclude that, when orthotopic corneal allografts are accepted indefinitely by adult mice, graft success correlates with the induction of alloantigenically specific anterior chamber-associated immune deviation. It is proposed that suppression of alloantigen-specific DH, which is characteristic of mice with accepted grafts, plays a critical role in the success of grafted corneas.