MECHANISMS OF CORNEA ALLOGRAFT REJECTION & ENHANCEMENT

该项目的长期目标是了解以下因素 促进角膜移植的同种异体，并确定可能的机制 因此移植物存活率可以通过免疫操作提高移植物的存活率 宿主或供体角膜。 尽管角膜移植是一种常见且非常成功的方法 治疗由于角膜功能不全而导致的失明，估计超过 在美国，每年有2500例角膜移植被拒绝。此外， 免疫宿主对角膜的致敏和应答机制 组织仍不清楚。使用PVG.R1和PVG.1A型同源大鼠品系 与PVG株仅在主要的I类MHC基因座(RT1.A)和 我们最近分别对整个大鼠的MHC进行了表征： 体液和细胞对完整的同种异体角膜的反应性 及其分离成分；MHC抗原的表达 在大鼠角膜中的表达；I类和类的相对影响 II MHC抗原在诱导同种异体反应中在角膜中的表达。 建议进行实验以确定MHC抗原的表达和 在这个模型中，角膜的免疫原性可以通过以下处理来影响 已知的MHC抗原调节剂，如高压氧，抗供体I类 和II类MHC单抗和同种异体淋巴细胞。 同样，使用捐献者血液的受者治疗的潜在效果 输血和抗供体MHC抗血清将在以下方面进行检查 通过降低宿主反应性或供体角膜来提高移植物存活率 免疫原性。最后，我们将采用体内收养的组合 转移和体外第三方MLC/CML研究以检测细胞 以及参与这些同种异体角膜移植模型的分子机制 拒绝和增强。

The long term objectives of this project are to understand the factors that contribute to corneal graft allogenicity, and identify potential mechanisms whereby graft survival can be enhanced by immunologic manipulation of the host or donor cornea. Although corneal transplantation is a common and highly successful means of treating blindness due to corneal incompetence, it is estimated that over 2500 corneal grafts are rejected in the U.S. annually. In addition, the mechanisms of immunologic host sensitization and responsiveness to corneal tissue remain unclear. Using PVG.R1 and PVG.1A congenic rat strains which differ from the PVG strain only at the major class I MHC locus (RT1.A) and the entire rat MHC respectively, we have recently characterized: the nature of humoral and cellular responsiveness to intact allogeneic cornea as well as its separate components; the expression of MHC antigen expression in rat corneas; and the relative influence of class I and class II MHC antigens expression in the cornea on inducing allogeneic responses. Experiments are proposed to determine whether MHC antigen expression and corneal immunogenicity can be affected in this model by treatments with known MHC antigen modulators such as hyperbaric oxygen, anti-donor class I and class II MHC monoclonal antibodies, and allogeneic lymphocytes. Similarly, the potential effects of recipient therapy using donor blood transfusions and anti-donor MHC antisera will be examined in terms of enhancing graft survival by reducing host responsiveness or donor cornea immunogenicity. Finally, we will employ a combination of in vivo adoptive transfer and in vitro third party MLC/CML studies to examine the cellular and molecular mechanisms involved in these models of corneal allograft rejection and enhancement.