'Subthreshold stimulation' of allospecific delayed hypersensitivity by corneal allografts

Corneal allografts contain few or no Ia+ Langerhans' cells and consistently fail to elicit allospecific delayed-type hypersensitivity (DTH). The present study examined the hypothesis that the inability of corneal allografts to induce allospecific DTH was the result of active suppression. However, the results indicated that an initial exposure to corneal allografts provided a subthreshold stimulus for the induction of DTH because hosts that received a second pair of corneal grafts 7 days later developed DTH. By contrast, hosts that received all four corneal allografts simultaneously, failed to display DTH to donor alloantigens. Hosts that received a single set of corneal allografts did not display DTH to donor alloantigens, yet their spleen cells were capable of transferring DTH to hosts subsequently stimulated with a single set of corneal grafts. The capacity of Langerhans' cell-free corneal grafts to prime the host so that a second set of corneal grafts stimulated DTH to donor alloantigens was termed 'subthreshold stimulation of DTH'. The ability of sequential sets of corneal grafts to induce DTH was abolished by fixation with 0.2% paraformaldehyde. Surprisingly, the single cell-layered corneal endothelium was found to be the crucial corneal component necessary for the induction of allospecific DTH. This unique spectrum of corneal alloimmunogenicity may contribute to the immunological privilege and high success rate of corneal allografts.