MECHANISMS OF CORNEA ALLOGRAFT REJECTION & ENHANCEMENT

本项目的长期目标是了解 有助于角膜移植同种异体性，并确定潜在的机制 由此可以通过免疫学操作来增强移植物的存活， 宿主或供体角膜。 虽然角膜移植是一种常见的和非常成功的手段， 治疗由于角膜功能不全导致的失明，据估计， 在美国，每年有2500例角膜移植被排斥。 此外该 免疫宿主对角膜基质的致敏和反应机制 组织仍不清楚。 使用PVG.R1和PVG.1A同源大鼠品系， 仅在主要I类MHC基因座（RT1.A）上与PVG株不同， 整个大鼠MHC分别，我们最近的特点： 同种异体完整角膜的体液和细胞反应性 以及其单独的成分; MHC抗原的表达 在大鼠角膜中的表达;以及I类和II类的相对影响。 II.角膜中MHC抗原的表达对诱导同种异体反应的影响。 提出实验来确定是否MHC抗原表达和 在该模型中，角膜免疫原性可受到以下治疗的影响： 已知的MHC抗原调节剂如高压氧、抗供体I类 和II类MHC单克隆抗体，以及同种异体淋巴细胞。 同样，使用供体血液的受体治疗的潜在影响 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提高移植物存活率 免疫原性 最后，我们将采用体内过继 转移和体外第三方MLC/CML研究， 以及这些角膜移植模型的分子机制 抑制和增强。

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.