Fate of MHC-matched corneal allografts in Th1-deficient hosts.
OBJECTIVE
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.
Hargrave
Sylvia L
SL
Department of Ophthalmology, University of Texas, Southwestern Medical Center, Dallas, Texas 75390-9057, USA.
Hay
Christina
C
Mellon
Jessamee
J
Mayhew
Elizabeth
E
Niederkorn
Jerry Y
JY
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003315:Cornea / Q000276:immunology*; D005260:Female; D006084:Graft Rejection / Q000276:immunology*; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D015948:Keratoplasty, Penetrating; D008285:Major Histocompatibility Complex / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D018345:Mice, Knockout; D016038:Skin Transplantation; D018417:Th1 Cells / Q000276:immunology*; D014184:Transplantation, Homologous
D000911:Antibodies, Monoclonal; D007371:Interferon-gamma