OCULAR MECHANISMS OF REJECTION OF CORNEAL ENDOTHELIUM

免疫排斥反应是角膜移植术后晚期失败的主要原因 移植物，最常见于已经血管化的高危受者 角膜或患有前段慢性炎症性疾病。 的 在至少一半的临床疾病中，内皮是主要受影响的组织。 角膜移植排斥反应 II类同种异体抗原的表达 （人类HLA-DP，-DQ，-DR;动物Ia）可由γ- 干扰素作用于包括角膜内皮在内的多种靶细胞 （Donnelly等人，Invest Ophth维斯科学26：575; Young等人，投资Ophth 维斯科学26：570; 1985）。 眼前节免疫原性炎症 眼内伴有局部产生的Ia诱导 角膜内皮细胞Ia抗原的表达 （Donnelly和Prendergast，Cell Immunol 86：557，1984; Donnelly等人，op. cit.）。 移植角膜上的II类同种异体抗原表达可以增加 内皮激发局部免疫应答的潜力，和/或 它对免疫效应物溶解的敏感性。 在这种情况下， 高风险临床角膜移植的成功概率为 通过匹配II类同种异体抗原或通过抑制 在供体角膜上诱导这些抗原。 目前的研究将详细定义当地的时间进程， Ia诱导的淋巴因子产生和内皮细胞Ia表达 兔角膜原位移植排斥反应的研究 的能力 的Ia-轴承内皮细胞启动传入肢体的免疫 通过诱导辅助性T淋巴细胞增殖，诱导 同种特异性溶细胞性T淋巴细胞（CTL）的形成，以及加工和 将同种抗原呈递给辅助性T细胞和CTL，将在一项研究中确定。 近交系小鼠体外模型。 载Ia角膜的易感性 内皮细胞被CTL裂解，代表免疫球蛋白的传出支。 也将在体外小鼠模型中确定响应。 这些发现 在动物模型中，将与人角膜移植排斥反应相关 免疫组化法检测排斥反应中DR和DP/DQ抗原 角膜和慢性发炎眼睛的角膜。

Immunological rejection is the leading cause of late failure of corneal grafts, most commonly in high-risk recipients with already vascularized corneas or with chronic inflammatory disease of the anterior segment. The endothelium is the principally affected tissue in at least half of clinical corneal allograft rejections. The expression of Class II alloantigens (HLA-DP, -DQ, -DR in humans; Ia in animals) may be induced by gamma interferon on a variety of target cells including corneal endothelium (Donnelly et al, Invest Ophth Vis Sci 26:575; Young et al., Invest Ophth Vis Sci 26:570; 1985). Immunogenic inflammation in the anterior segment of the eye is accompanied by the local production of Ia-inducing lymphokines,and the expression of Ia antigens on corneal endothelium (Donnelly and Prendergast, Cell Immunol 86:557, 1984; Donnelly et al., op. cit.). Class II alloantigen expression on a grafted cornea could increase the potential of the endothelium to excite local immune responses, and/or its susceptibility to lysis by immune effectors. In this event, the probability of success of high-risk clinical corneal grafts would be improved by matching for Class II alloantigens, or by inhibiting the induction of these antigens on the donor cornea. The present studies will define in detail the time course of local Ia-inducing lymphokine production and endothelial Ia expression during the rejection of orthotopic corneal allografts in a rabbit model. The ability of Ia-bearing endothelial cells to initiate the afferent limb of the immune response by inducing helper T lymphocyte proliferation, inducing the formation of allospecific cytolytic T lymphocytes (CTL), and processing and presenting alloantigens to helper T cells and CTL, will be determined in an inbred mouse in vitro model. The susceptibility of Ia-bearing corneal endothelium to lysis by CTL, representing the efferent limb of the immune response, also will be determined in an in vitro mouse model. The findings in animal models will be correlated with human corneal allograft rejection by immunohistochemical staining of DR and DP/DQ antigens in rejected corneas and in corneas from chronically inflamed eyes.