title: Preservation of donor cornea prevents corneal allograft rejection by inhibiting induction of alloimmunity.
abstract: To determine whether preservation of the donor cornea prevents allograft rejection, orthotopic corneal transplantation was performed using corneas preserved in storage medium (Optisol-GS((R))). Donor corneas harvested from C3H/He (H-2(k)) mice and B10.D2 (H-2(d)) mice were preserved in storage medium for 0, 3, 7 and 14 days, and then transplanted into the corneal beds of the recipient BALB/c (H-2(d)) mice. Graft survival was determined clinically and histologically. The expression of major histocompatibility complex (MHC) molecules in the preserved corneas was analysed by immunohistochemistry and Western blotting. Donor-specific cytotoxic T lymphocyte (CTL) and delayed-type hypersensitivity (DTH) responses were assessed 3 weeks after grafting. Active suppression of DTH in the recipient mice was also examined 3 weeks after grafting. The survival of 14 day preserved allografts was significantly higher than that of the non-preserved allografts in both MHC and minor histocompatibility (H) antigens, and minor H only disparate combination. The recipients of the preserved allografts failed to induce both CTL and DTH. The active suppression of DTH was not acquired in these recipients. The expression of donor-derived MHC class I antigens was markedly reduced in the corneas after preservation. Preservation of the donor cornea had a remarkable effect on the prevention of corneal allograft rejection. Since the preserved allografts failed to induce donor-specific CTL and DTH, and active suppression of DTH was not acquired in the recipients, the prevention of allo-rejection is due to a failure of allo-sensitization. These results indicate that the reduction of MHC class I antigens and minor H antigens expression in the preserved grafts induces a failure of allo-sensitization and leads to the high rate of acceptance in corneal allografts.
authors.affiliation: Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, Japan. KAMIYA-OPH@h.u-tokyo.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Kamiya
authors.forename: J
authors.initials: J
authors.lastname: Hori
authors.forename: F
authors.initials: F
authors.lastname: Kagaya
authors.forename: T
authors.initials: T
authors.lastname: Usui
authors.forename: S
authors.initials: S
authors.lastname: Amano
authors.forename: T
authors.initials: T
authors.lastname: Oshika
authors.forename: T
authors.initials: T
authors.lastname: Mizouchi
authors.forename: T
authors.initials: T
authors.lastname: Tsuru
authors.forename: S
authors.initials: S
authors.lastname: Yamagami
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D003315:Cornea / Q000276:immunology; D016039:Corneal Transplantation / Q000379:methods*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008815:Mice, Inbred Strains; D018709:Statistics, Nonparametric; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014021:Tissue Preservation / Q000379:methods; D014184:Transplantation, Homologous
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II