The effect of tissue dose and site of grafting on immunity to corneal allografts.

The purpose of this investigation was to determine the quantitative relationship between corneal alloantigens and host immunity. In addition, the effect of the site of introduction of the corneal antigens on the host response was determined. Two alloantigenic strains of rats were reciprocally grafted at three different locations in the body with carefully quantitated amounts of corneal tissue: (1) orthotopically in the cornea of the eye; (2) subcutaneously; and (3) intraperitoneally. Corneal tissue placed orthotopically into vascularized graft beds did not elicit a systemic immune response. Subcutaneous grafts elicited a weak systemic alloantigenic response, whereas corneal tissue placed in the peritoneal cavity consistently induced a vigorous cellular and humoral alloantigenic response. Eight or more full thickness corneal allografts grafted subcutaneously were required to elicit a systemic response. On the other hand, as few as four corneal allografts placed intraperitoneally invariably elicited a systemic alloimmune response. The results of this investigation demonstrate that both the amount and route of introduction of alloantigen affect the recipient's response to corneal tissue and that the rejection of a single orthotopic cornea graft is a site-limited response. Immune effector cells were not found in the spleens and alloantibodies were not present in the serum of animals that had rejected corneal allografts.