Thiol redox and immune regulation in corneal transplantation.
Penetrating keratoplasty (PKP) is the most common type of clinical grafting performed in humans. Although PKP has emerged as the most successful form of transplantation, PKP in "high-risk" eyes shows high incidence of allograft rejection. The incidence of epithelial rejection after limbal transplantation (LT) is extremely higher and swifter than PKP rejection, and even intensive systemic immunosuppressive therapy is often of no avail. Because failure of corneal grafts is an important cause of blindness, developing new strategies for suppressing graft rejection is a worthy goal for research. Corneal allograft rejection is mainly mediated by the TH1-type immune response, which leads to a delayed-type hypersensitivity reaction. Because the TH2-type immune response regulates the TH1-type immune response, we have successfully elicited allograft survival after both PKP and LT by inducing systemic TH2-type immune responses. Because intracellular thiol redox status of antigen-presenting cells (APC) reportedly regulates TH1/TH2 balance via distinctive cytokine production by APC, we also investigated the effect of modulating macrophage intracellular thiol redox status on corneal allograft survival. These strategies are quite effective in major histocompatibility complex (MHC) matching in mice, although it is believed that MHC matching has no effect on corneal allograft survival according to many rodent studies. Recently, many laboratories are reconsidering HLA matching for allograft survival in human corneal transplantation. It may be possible that MHC matching improves corneal allograft survival in the context of TH1 suppression. We propose that the suppression of the TH1-type immune response and MHC matching together may promote allograft survival in humans.
Yamada
Jun
J
Department of Ophthalmology, Meiji University of Oriental Medicine, Kyoto, Japan. jyamada@opth.kpu-m.ac.kp
D000818:Animals; D016039:Corneal Transplantation / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival; D006433:Hemocyanins / Q000276:immunology; D006648:Histocompatibility; D006649:Histocompatibility Antigens / Q000032:analysis / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D015948:Keratoplasty, Penetrating / Q000276:immunology; D016850:Limbus Corneae / Q000601:surgery; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010084:Oxidation-Reduction; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
D006649:Histocompatibility Antigens; D013438:Sulfhydryl Compounds; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin