MECHANISMS OF CORNEAL ALLOGRAFT REJECTION

该项目将检查几个遗传和免疫参数， 人类角膜移植受者，以探索可能的相关性， 同种异体移植排斥反应。 具体来说，排斥风险高的患者 由于角膜血管化或先前的移植物丢失， ABO血型，供者淋巴细胞交叉配型阴性移植物， 评估前瞻性HLA-A、-B、-C和-DR匹配的益处。 都很高- 低风险患者将在移植前进行筛查， 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。 在移植后和排斥反应期间将进行类似的评估 情节。 供体特异性反应性将通过使用 供体角膜环与受体间接免疫荧光 血清的 抗体的检测和表征将使用 灵敏的微细胞毒性和抗原结合试验， 某些功能特征是否与排斥有关。 宿主细胞免疫也将使用淋巴细胞介导的 对人淋巴细胞、角膜细胞和血管的细胞毒性 内皮细胞 新鲜的和培养的人角膜内皮细胞将 使用多种免疫组织化学方法检测各种抗原的表达。 血清学测定。 单克隆以及异源和异源血清 HLA抗原、淋巴细胞分化特异性试剂 抗原和血管内皮/单核细胞抗原，将用于 表征这样的角膜内皮标记物。 这些研究建议 以：1）确定预期的HLA-A、-B、-C和-DR供体-受体是否 配型对交叉配型阴性的高危角膜移植物有益 患者; 2）确定是否有任何可检测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质 其是免疫介导的移植排斥的重要靶点。

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.