UVB irradiation renders corneal allografts tolerogenic for allospecific delayed hypersensitivity responses

Heterotopic corneal allografts treated with ultraviolet (UV) radiation not only failed to elicit allospecific delayed-type hypersensitivity (DTH) responses in mice but rendered the hosts tolerant to subsequent immunization with normally immunogenic corneal allografts. The immunological tolerance induced by UV-treated grafts was cyclophosphamide sensitive and antigen specific. Adoptive transfer studies revealed that the tolerance to donor alloantigens could be transferred with CD4+, CD8- T cells which suppressed alloimmune DTH responses at the afferent but not the efferent limb. The capacity of UV-treated corneal allografts to induce allospecific tolerance was related to UV irradiation and not simply a result of loss of corneal viability. Formalin-fixed corneal allografts could not produce similar tolerization for DTH responses. Selective debridement of either the corneal epithelium or endothelium revealed that the corneal endothelium was the critical layer necessary for UV-dependent tolerance induction. Furthermore, the initial exposure to UV irradiation must occur through the endothelium and not the epithelium. Thus, the single-cell layered corneal endothelium is the target for the immunomodulatory effects of UV irradiation on corneal allografts.