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(Investigative Ophthalmology and Visual Science. 2004;45:1188-1193.)
© 2004 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.03-0515
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Fate of MHC-Matched Corneal Allografts in Th1-Deficient Hosts

Sylvia L. Hargrave, Christina Hay, Jessamee Mellon, Elizabeth Mayhew, and Jerry Y. Niederkorn

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

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.




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J. Yamada, J. Hamuro, A. Fukushima, T. Ohteki, K. Terai, Y. Iwakura, H. Yagita, and S. Kinoshita
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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
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