title: The effect of oral immunization on corneal allograft survival.
abstract: The present study examined the potential of orally induced tolerance for preventing immunological rejection of corneal allografts. Orthotopic corneal allografts were transplanted from either C3H (MHC + multiple minor H-mismatched) or NZB (multiple minor H-mismatched only) donors to CB6F1 recipients on day 0. Tissue cultured corneal epithelial and endothelial cells from relevant donor strains were administered orally from day -14 to day -4 on a daily basis, The incidence of graft rejection, graft mean survival time (MST), and alloimmune responses, and the antigen specificity of induced tolerance were studied. Oral immunization induced a remarkable tolerance such that only 55% of the orally immunized hosts rejected their fully allogeneic corneal grafts (MST = 43 days) compared with 100% rejection (MST = 18 days) in normal controls. Likewise, rejection of MHC-matched, multiple minor H-mismatched corneal grafts fell from 80% in untreated controls to 36% in orally immunized hosts. Oral immunization was effective in desensitizing previously immunized hosts. Rejection of MHC-matched, multiple H minor-mismatched corneal allografts fell from 93% in preimmune, unfed hosts to 36% in preimmune, orally tolerized mice. Thus, oral immunization is a safe and effective method for desensitizing high-risk, preimmune hosts and promoting corneal allograft survival.
authors.affiliation: Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas, Texas 75235-057, USA.
authors.forename: Y G
authors.initials: YG
authors.lastname: He
authors.forename: J
authors.initials: J
authors.lastname: Mellon
authors.forename: J Y
authors.initials: JY
authors.lastname: Niederkorn
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003315:Cornea / Q000166:cytology / Q000276:immunology*; D016039:Corneal Transplantation / Q000276:immunology*; D004848:Epithelium / Q000276:immunology / Q000637:transplantation; D000939:Epitopes; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007114:Immunization; D007165:Immunosuppression Therapy / Q000379:methods*; D015994:Incidence; D007518:Isoantibodies / Q000096:biosynthesis; D007519:Isoantigens / Q000627:therapeutic use; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008814:Mice, Inbred NZB; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D000939:Epitopes; D007518:Isoantibodies; D007519:Isoantigens