Fate of MHC-matched corneal allografts in Th1-deficient hosts

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.