IMMUNOBIOLOGY OF CORNEAL TRANSPLANTATION

角膜移植的免疫生物学

• 批准号: 7221202
• 负责人: Bruce R Ksander
• 金额: $ 42.82万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7221202
• 关键词: Alloantigen; Allografting; Beds; CD8B1 gene; Cells; Class; Clinical; Cornea; Corneal Endothelium; Data; Endothelium; Epithelium; Eye; Failure; Goals; Graft Survival; Human; Immune; Immunobiology; Keratoplasty; Kidney; MHC Class I Genes; MHC Class II Genes; Mediator of activation protein; Minor; Molecular; Mus; Penetrating Keratoplasty; Protocols documentation; Risk; Role; T-Lymphocyte; TNFSF6 gene; Tissues; base; capsule; corneal allograft; corneal epithelium; graft failure; novel; research study

DESCRIPTION: Whereas many primary, penetrating keratoplasties succeed in humans, an intolerably high proportion fails in "high-risk" eyes. Immune rejection is the major cause of allograft failure. Our long-term goals are to understand: (a) why primary orthotopic corneal allografts are so well tolerated (display immune privilege), and (b) why grafts in "high-risk" eyes fare so poorly. During the past 5 years we have made progress toward these goals by demonstrating that: (a) MHC class II and minor H, but not MHC class I, alloantigens are important barriers to corneal allograft acceptance, (b) direct and indirect alloreactive CD4+, but not CD8+, T cells are the dominant mediators of rejection, and (c) comeal endothelium, in part through expression of CD95L, displays inherent immune privilege. Based upon these findings, we have formulated two related hypotheses to guide our experiments: Hypothesis 1. Atypical expression of alloantigens and expression of immunomodulatory molecules on corneal cells contribute to the cornea's immune privileged status. These experiments will determine if expression of alloantigens and/or immunomodulatory molecules on corneal cells, rather than the special qualities of the surrounding graft bed in the eye, contributes to the cornea's status as an immune privileged tissue. Hypothesis 2. MHC class II and/or minor H alloantigen expression rob the corneal epithelium of its graft-acceptance promoting capacity. Our previous data indicated that syngeneic epithelium makes a positive contribution to immune privilege for orthotopic corneal allografts. These experiments will utilize composite comeal grafts composed of recipient epithelium layered over donor stroma/endothelium (and visa versa). We will determine the capacity of composite corneal allografts to induce allosensitization. Our experiments will enable us to discover novel cellular and molecular mechanisms with which to create protocols with greater power to promote graft acceptance in clinical situations where graft failure is all too common.

描述：虽然许多主要的，穿透性角色塑料在人类中取得了成功，但“高风险”的眼睛中的不可分比的比例失败了。免疫排斥是同种异体移植失败的主要原因。我们的长期目标是理解：（a）为什么耐受性耐受性（表现出免疫特权），以及（b）为什么“高风险”眼睛中的移植物的出现如此差。 During the past 5 years we have made progress toward these goals by demonstrating that: (a) MHC class II and minor H, but not MHC class I, alloantigens are important barriers to corneal allograft acceptance, (b) direct and indirect alloreactive CD4+, but not CD8+, T cells are the dominant mediators of rejection, and (c) comeal endothelium, in part through expression of CD95L, displays inherent immune 特权。基于这些发现，我们提出了两个相关的假设来指导我们的实验：假设1。同种抗原的非典型表达以及角膜细胞上免疫调节分子的表达，有助于角膜的免疫特权状态。这些实验将确定角膜细胞上同种抗菌素和/或免疫调节分子的表达，而不是眼中周围移植床的特殊质量，这有助于角膜作为免疫特权组织的地位。假设2。MHC II类和/或次要H同具有同具有的表达，将其移植感受感知能力促进能力的角膜上皮。我们以前的数据表明，同性上皮对原位角膜同种异体移植物的免疫特权做出了积极的贡献。这些实验将利用由供体基质/内皮（以及Visa Versa）上层层的受体上皮组成的复合comeal移植物。我们将确定复合角膜同种异体移植物诱导异敏化的能力。我们的实验将使我们能够发现新颖的细胞和分子机制，在该方案中创建具有更大功能的方案，以在移植失败非常普遍的临床情况下促进移植物接受。