The relative immunogenicity of corneal epithelium, stroma, and endothelium. The role of major histocompatibility complex antigens

Corneal allografts have been shown to give rise to immune responses, but the role and relative importance of individual corneal cell populations in evoking such responses remain unclear. We dissected ACI (RT1^a) rat corneas into separate epithelial, stromal, and endothelial components by a method that yields pure cell populations in tissue culture, and grafted these components separately to groups of fully allogeneic PVG (RT1(c)) recipients. Grafts of corneal stroma elicited strong cellular cytotoxic immune responses in a cell-mediated lymphocytotoxic assay, but corneal epithelium failed to generate any detectable response. Grafts of corneal endothelium alone, however, evoked a potent cellular cytotoxic response. Using congenic rats, it was found that grafts from PVG.1A (RT1^a) donors to PVG (RT1(c)) recipients (which differ at both the RT1.A and B loci) yielded identical results. However, no corneal component graft from PVG.R1 (RT1(rl)) donors to PVG recipients (which differ only at RT1.A) generated a detectable immune response. Use of target lymphoblasts from congenic strains established that at least part of all responses detected were directed against class I (RT1.A) major histocompatibility complex antigens. These findings indicate that there is differential immunogenicity of specific corneal tissue components in the rat that may be further influenced by the degree of MHC disparity between donor and recipient.