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Fate of MHC-Matched Corneal Allografts in Th1-Deficient Hosts

From the Department of Ophthalmology, University of Texas, Southwestern Medical Center, Dallas, Texas.

PURPOSE. To determine whether the Th1 cytokine, interferon (IFN)-, is necessary for corneal graft rejection.

METHODS. Full-thickness penetrating keratoplasties were performed in normal mice and in IFN- knockout (KO) mice.

RESULTS. Sixty-four percent of the MHC-mismatched corneal allografts were rejected in IFN- 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- KO mice or the wild-type mice treated with anti-IFN- monoclonal antibody. Corneal graft rejection in IFN-–deficient hosts was characterized by an eosinophilic infiltrate compared with a mononuclear inflammatory infiltrate in normal mice.

CONCLUSIONS. IFN- is not necessary for the rejection of MHC-mismatched corneal grafts. However, IFN- 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- KO mice, is characterized by cross-regulation of Th1 cytokines, such as IFN-. The present results indicate that MHC matching dramatically reduces the risk of corneal graft rejection when IFN- is depressed or absent. Thus, MHC matching may reduce the risk of corneal graft rejection in patients with atopic keratoconus.

This article has been cited by other articles:

				C. Beauregard, C. Stevens, E. Mayhew, and J. Y. Niederkorn Cutting Edge: Atopy Promotes Th2 Responses to Alloantigens and Increases the Incidence and Tempo of Corneal Allograft Rejection J. Immunol., June 1, 2005; 174(11): 6577 - 6581. [Abstract] [Full Text] [PDF]