IMMUNOBIOLOGY OF CORNEAL TRANSPLANATION

而绝大多数的初级角膜成形术在人类 人类，无法忍受的高比例异体角膜移植 进入“高风险”的眼睛失明。免疫排斥被认为是主要的 移植失败的原因。我们的长期目标是了解细胞 以及分子免疫过程决定了(A)为什么原发原位移植 同种异体角膜移植的耐受性如此之好，以及(B)为什么在 “高风险”眼睛的情况非常糟糕。我们的实验方法是进行 并分析近交系小鼠的同种异体角膜移植。至 为了指导我们的实验，我们提出了两个相关的假设： (1)由于正常角膜缺乏专业抗原 提呈细胞，诱导对同种异体抗原的系统免疫 几乎完全通过受体抗原进行原位角膜移植 提呈细胞--所谓的抗原间接途径 演示文稿。 (2)高危眼的同种异体移植更容易发生排斥反应 因为眼组织，包括角膜本身，不能提供 免疫抑制的眼内微环境。 我们描述了三个具体目标： 1.评估不同程度的免疫遗传之间的相互作用 同种异体角膜移植物返流的差异及危险因素 在老鼠身上。 2.确定T细胞识别同种异体抗原的途径 在原位角膜移植上。 3.确定眼组织，特别是角膜组织在多大程度上 “高危”眼睛不能产生并维持局部免疫抑制 微环境。 我们的实验将产生结果，这应该有助于阐明 免疫特免权在角膜整形手术中的非凡成功， 将特权的丧失归因于“高风险”眼睛，并将 使关键同种异体抗原的免疫原性降至最低 移植物衰竭。

Whereas the great majority of primary keratoplasties succeed in human beings, and intolerable high proportion of allogeneic corneas grafter into"high-risk" eyes fail. Immune rejection is regarded as the major cause of graft failure. Our long term goal is to understand the cellular and molecular immune processes that dictate (a) why primary orthotopic corneal allografts are so well tolerated, and (b) why grafts placed in "high-risk" eyes fare so poorly. Our experimental approach is to conduct and analyze orthotopic corneal allografts in inbred strains of mice. To guide us in our experiments, we have formulated two related hypotheses: (1) Because the normal cornea is deficient in professional antigen presenting cells, induction of systemic immunity to alloantigens on orthotopic corneal grafts occurs almost exclusively via recipient antigen presenting cells - the so-called indirect pathway of antigen presentation. (2) allografts are more likely to suffer rejection in high-risk eyes because the ocular tissues, including the cornea itself, fail to provide an immunosuppressive intraocular microenvironment. We describe three Specific Aims: 1. Evaluate interactions between varying degrees of immunogenetic disparity and risk factors for refection of orthotopic corneal allografts in mice. 2. Delineate pathways of T cell recognition of alloantigens expressed on orthotopic corneal grafts. 3. Determine the extent to which ocular tissues, especially cornea, of "high-risk" eyes fail to create and sustain a local immunosuppressive microenvironment. Our experiments will generate results that should help to elucidate the roe of immune privilege in the extraordinary success of keratoplasties, the contribution that loss of privilege to "high-risk" eyes, and would minimize the immunogenicity of the critical alloantigens responsible for graft failure.