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Sylvia L. Hargrave, Christina Hay, Jessamee Mellon, Elizabeth Mayhew, Jerry Y. Niederkorn; Fate of MHC-Matched Corneal Allografts in Th1-Deficient Hosts. Invest. Ophthalmol. Vis. Sci. 2004;45(4):1188-1193. doi: 10.1167/iovs.03-0515.
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purpose. To determine whether the Th1 cytokine, interferon (IFN)-γ, is necessary for corneal graft rejection.
methods. Full-thickness penetrating keratoplasties were performed in normal mice and in IFN-γ knockout (KO) mice.
results. Sixty-four percent of the MHC-mismatched corneal allografts were rejected in IFN-γ 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-γ KO mice or the wild-type mice treated with anti-IFN-γ monoclonal antibody. Corneal graft rejection in IFN-γ–deficient hosts was characterized by an eosinophilic infiltrate compared with a mononuclear inflammatory infiltrate in normal mice.
conclusions. IFN-γ is not necessary for the rejection of MHC-mismatched corneal grafts. However, IFN-γ 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-γ KO mice, is characterized by cross-regulation of Th1 cytokines, such as IFN-γ. The present results indicate that MHC matching dramatically reduces the risk of corneal graft rejection when IFN-γ is depressed or absent. Thus, MHC matching may reduce the risk of corneal graft rejection in patients with atopic keratoconus.
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