Hargrave Sylvia L, Hay Christina, Mellon Jessamee, Mayhew Elizabeth, Niederkorn Jerry Y
Department of Ophthalmology, University of Texas, Southwestern Medical Center, Dallas, Texas 75390-9057, USA.
Invest Ophthalmol Vis Sci. 2004 Apr;45(4):1188-93. doi: 10.1167/iovs.03-0515.
To determine whether the Th1 cytokine, interferon (IFN)-gamma, is necessary for corneal graft rejection.
Full-thickness penetrating keratoplasties were performed in normal mice and in IFN-gamma knockout (KO) mice.
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.
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.
确定Th1细胞因子干扰素（IFN）-γ对于角膜移植排斥反应是否必要。
在正常小鼠和IFN-γ基因敲除（KO）小鼠中进行全层穿透性角膜移植术。
在IFN-γ KO小鼠中，64%的MHC不匹配角膜同种异体移植被排斥。相比之下，MHC匹配的角膜同种异体移植在50%至77%的野生型宿主中被排斥，但在任何IFN-γ KO小鼠或用抗IFN-γ单克隆抗体处理的野生型小鼠中均未被排斥。与正常小鼠中的单核炎性浸润相比，IFN-γ缺陷宿主中的角膜移植排斥以嗜酸性粒细胞浸润为特征。
IFN-γ对于MHC不匹配角膜移植的排斥并非必要。然而，IFN-γ和Th1免疫机制对于MHC匹配的角膜同种异体移植的排斥是必要的，这些移植使宿主面对外来次要组织相容性抗原。与IFN-γ KO小鼠一样，特应性患者的免疫反应以Th1细胞因子如IFN-γ的交叉调节为特征。目前的结果表明，当IFN-γ降低或缺乏时，MHC匹配可显著降低角膜移植排斥的风险。因此，MHC匹配可能降低特应性圆锥角膜患者角膜移植排斥的风险。
