MECHANISMS OF CORNEAL ALLOGRAFT REJECTION

该项目将检查几个遗传和免疫学参数 探讨人类角膜移植受者与 同种异体排斥反应。具体地说，排斥反应的高危患者 由于角膜血管形成或之前的移植物丢失，将仅接受 ABO血型，供者淋巴细胞交叉配型阴性移植物 评估预期的人类白细胞抗原-A、-B、-C和-DR配型的益处。两者都很高- 低风险患者将在移植前进行筛查，以确定是否存在 组织相容性抗原抗体、淋巴细胞分化 标记物、血管内皮抗原和角膜组织抗原。 类似的评估将在移植后和排斥期间进行。 剧集。将通过使用一种 供体角膜环与受体的间接免疫荧光 血清。抗体的检测和表征将使用 敏感的微量细胞毒性和抗原结合试验均可确定 某些功能特征是否与排斥反应相关。 宿主细胞免疫也将通过淋巴细胞介导的方式进行检测。 对人淋巴细胞、角膜细胞和血管的细胞毒作用 内皮细胞。新鲜的和培养的人角膜内皮细胞都会 使用各种不同的方法检测各种抗原的表达 血清学检测。单抗，以及同种和异种血清 对人类白细胞抗原、淋巴细胞分化具有特异性的试剂 抗原和血管内皮细胞/单核细胞抗原将用于 这些角膜内皮标志物的特征。这些研究是提出的 以：1)确定预期的人类白细胞抗原-A、-B、-C和-DR供受者 配型有利于交叉配型阴性的高危同种异体角膜移植 患者；2)确定是否有任何可检测到的血清学或细胞参数 免疫在预测最终移植物中具有诊断或预后价值 排斥反应；3)确定角膜内皮的抗原性 它是免疫介导的移植物排斥反应的重要靶点。

This project will examine several genetic and immunologic parameters in human corneal transplant recipients to explore possible correlations with allograft rejection. Specifically, patients at high risk for rejection because of corneal vascularization or prior graft loss will receive only ABO blood group, donor-lymphocyte crossmatch negative grafts with the benefit of prospective HLA-A,-B,-C and -DR matching evaluated. Both high- and low-risk patients will be screened prior to grafting for the persence of antibodies to histocompatibility antigens, lymphocyte differentiation markers, vascular endothelium antigens, and corneal tissue antigens. Similar evaluation will be performed post-transplant and during rejection episodes. Donor-specific reactivity will be assessed by utilizing an annulus of donor cornea for indirect immunofluorescence with recipient serum. Detection and characterization of antibodies will be made using both sensitive microcytotoxicity and antigen binding assays to determine whether certain functional characteristics may correlate with rejection. Host cellular immunity will also be examined using lymphocyte mediated cytotoxicity against human lymphocytes, corneal cells and vascular endothelium. Both fresh and cultured human corneal endothelial cells will be examined for the expression of various antigens using a variety of serologic assays. Monoclonal, as well as isologous and heterologous serum reagents with specificity for HLA antigens, lymphocyte differentiation antigens, and vascular endothelium/monocyte antigens, will be used to characterize such corneal endothelial markers. These studies are proposed to: 1) determine if prospective HLA-A,-B,-C and -DR donor-recipient matching is of benefit in crossmatch negative high-risk corneal allograft patients; 2) determine if any detectable serologic or cellular parameter of immunity is of diagnostic or prognostic value in predicting eventual graft rejection; 3) determine the antigenic nature of the corneal endothelium which is an important target for immune mediated graft rejection.