Author(s): Hargrave SL, Hay C, Mellon J, Mayhew E, Niederkorn JY
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Abstract PURPOSE: To determine whether the Th1 cytokine, interferon (IFN)-gamma, is necessary for corneal graft rejection. METHODS: Full-thickness penetrating keratoplasties were performed in normal mice and in IFN-gamma knockout (KO) mice. RESULTS: Sixty-four percent of the MHC-mismatched corneal allografts were rejected in IFN-gamma KO mice. By contrast, MHC-matched corneal allografts were rejected in 50\% to 77\% of the wild-type hosts, but were not rejected in any of the IFN-gamma KO mice or the wild-type mice treated with anti-IFN-gamma monoclonal antibody. Corneal graft rejection in IFN-gamma-deficient hosts was characterized by an eosinophilic infiltrate compared with a mononuclear inflammatory infiltrate in normal mice. CONCLUSIONS: IFN-gamma is not necessary for the rejection of MHC-mismatched corneal grafts. However, IFN-gamma and Th1 immune mechanisms are necessary for the rejection of MHC-matched corneal allografts that confront the host with foreign minor histocompatibility antigens. The immune response in atopic patients, as in IFN-gamma KO mice, is characterized by cross-regulation of Th1 cytokines, such as IFN-gamma. The present results indicate that MHC matching dramatically reduces the risk of corneal graft rejection when IFN-gamma is depressed or absent. Thus, MHC matching may reduce the risk of corneal graft rejection in patients with atopic keratoconus.
This article was published in Invest Ophthalmol Vis Sci
and referenced in Journal of Clinical & Experimental Ophthalmology