Verhagen C, Mor F, Kipp J B, de Vos A F, van der Gaag R, Cohen I R
Department of Ophthalmology, Academic Medical Centre, University of Amsterdam, The Netherlands.
Invest Ophthalmol Vis Sci. 1999 Sep;40(10):2191-8.
Idiopathic inflammation of the cornea, keratitis, has been proposed to result from an autoimmune process, but thus far no convenient animal model of keratitis exists. An attempt was made to establish an animal model for keratitis, to investigate possible autoimmune mechanisms.
T-cell lines were established from lymph node cells removed from rats immunized with bovine corneal epithelium (BCE) extract. After restimulation in vitro with BCE or a specific corneal antigen, the cells were transferred by intraperitoneal injection into naive rats, rats subjected to total body irradiation, or rats in which only one eye was irradiated.
Neither direct immunization with corneal antigens nor transfer of activated anti-corneal T-cells into naive rats gave any signs of keratitis. Irradiation alone did not induce corneal inflammation. Transfer of corneal-specific activated T cells into irradiated rats produced keratitis starting around day 4 and culminating around day 8. The disease was self-limiting and the severity dependent on the dose and site of radiation. Keratitis was characterized by corneal haze, conjunctival and episcleral hyperemia, episcleral hemorrhages, chemosis, corneal infiltrates, and vascularization. Immunohistochemistry showed T-cell and macrophage infiltration of epithelium and stroma in the affected corneas.
Thus, keratitis may be produced by T cells reactive to corneal antigens, provided that the target tissue has been made susceptible by irradiation. The effectiveness of T-cell vaccination in preventing adoptive keratitis suggests that systemic as well as local tissue factors may regulate the disease process.
角膜的特发性炎症即角膜炎，被认为是由自身免疫过程引起的，但迄今为止尚无方便的角膜炎动物模型。本研究试图建立一种角膜炎动物模型，以探究可能的自身免疫机制。
从用牛角膜上皮（BCE）提取物免疫的大鼠身上取出淋巴结细胞，建立T细胞系。在用BCE或特定角膜抗原进行体外再刺激后，将细胞通过腹腔注射转移到未免疫的大鼠、接受全身照射的大鼠或仅一只眼睛接受照射的大鼠体内。
用角膜抗原直接免疫或向未免疫的大鼠转移活化的抗角膜T细胞均未出现角膜炎迹象。单独照射不会诱发角膜炎症。将角膜特异性活化T细胞转移到受照射的大鼠体内会在第4天左右引发角膜炎，并在第8天左右达到高峰。该疾病具有自限性，严重程度取决于辐射剂量和部位。角膜炎的特征为角膜混浊、结膜和巩膜充血、巩膜出血、球结膜水肿、角膜浸润和血管化。免疫组织化学显示，受影响角膜的上皮和基质中有T细胞和巨噬细胞浸润。
因此，只要靶组织因照射而变得易感，对角膜抗原反应的T细胞就可能引发角膜炎。T细胞疫苗接种在预防过继性角膜炎方面的有效性表明，全身以及局部组织因素可能调节疾病进程。
