OCULAR MECHANISMS OF REJECTION OF CORNEAL ENDOTHELIUM

免疫排斥是晚期角膜衰竭的主要原因 移植物，最常见于已有血管化的高危受者 角膜或前段慢性炎症性疾病。这个 在至少一半的临床病例中，内皮是主要的受累组织。 角膜移植排斥反应。第二类同种异体抗原的表达 (人类的HLA-DP、-DQ、-DR；动物的Ia)可能是由伽马诱导的 干扰素对包括角膜内皮在内的多种靶细胞的作用 (Donnelly等人，Invest Ophth Vis Sci 26：575；Young等人，Invest Ophth 《VIS科学》26：570；1985)。兔眼前段的免疫原性炎症 伴随眼睛的是局部产生的Ia诱导 淋巴因子与角膜内皮Ia抗原的表达 (Donnelly和Prendergast，细胞免疫86：557,1984；Donnelly等人，Op. 同上)。移植角膜上II类同种异体抗原的表达可能增加 血管内皮细胞激发局部免疫反应的潜力，和/或 它对免疫效应器裂解的敏感性。在这种情况下， 高危临床角膜移植的成功概率将是 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。 目前的研究将详细界定当地的时间进程 IA诱导的淋巴因子的产生和内皮Ia的表达 兔同种异体角膜移植排斥反应的实验研究一种能力 携带Ia的内皮细胞启动免疫的传入肢体 通过诱导辅助性T淋巴细胞增殖，诱导 同种异体特异性溶细胞T淋巴细胞(CTL)的形成、加工和 将同种异体抗原呈递给辅助T细胞和CTL，将在 近交系小鼠体外培养模型。含Ia的角膜易感性研究进展 内皮细胞被CTL溶解，代表免疫的传出肢体 反应，也将在体外小鼠模型中确定。调查结果 动物模型与人类同种异体角膜移植排斥反应相关 用免疫组织化学方法检测被拒患者的DR和DP/DQ抗原 角膜和慢性发炎眼的角膜中。

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.