INTESTINAL ALLOGRAFT REJECTION--MECHANISMS AND THERAPIES

描述（改编自申请人摘要）：虽然同种异体移植 排斥反应仍然是所有器官移植的障碍， 肠移植后排斥反应的严重程度是主要的 这是限制其在临床上成功应用的因素。 procedure. 这项研究建议是基于这样的假设， 同种异体肠移植物的性质与其他移植物不同， 机关 研究人员开发了一种新的小鼠肠道模型 移植来测试这一假设，使他们能够利用定义明确的 生物试剂和转基因株只适用于该物种。 他们的初步观察是，与先前描述的不同， 在其他器官移植的动物模型中，CD8 T细胞起着关键作用， 在肠排斥反应中的重要作用，使用体内单克隆 抗体消耗研究。 他们将描述CD8 T细胞的参与， 细胞在肠排斥反应中的作用，并比较CD8细胞在 从小肠到心脏移植排斥反应 在第二个观察中， 他们已经表明，在CD8 T细胞遗传缺陷的小鼠保留了 排斥肠移植的能力。 他们将通过以下方式研究该机制： 用抗CD8单克隆抗体治疗可以延长 肠同种异体移植物，并将其与CD8 敲除小鼠排斥相似的移植物。 最后，他们会利用 研究CD8 T细胞在排斥反应中发挥的独特作用 in vivo. 他们将直接检查共刺激需求， CD8 T细胞介导同种异体移植排斥反应的功能特性。

DESCRIPTION (Adapted from applicant's abstract): Although allograft rejection remains an obstacle for all organ transplants, the high incidence and severity of rejection following intestinal transplantation is the major factor limiting the uniform successful clinical application of this procedure. This research proposal is based on the hypothesis that rejection of intestinal allograft is qualitatively different from that of other organs. The investigators have developed a novel model of mouse intestine transplant to test this hypothesis, allowing them to utilize well-defined biological reagents and transgenic strains available only for this species. Their preliminary observation is that, distinct from previously described animal models of other organ transplants, CD8 T cells play a critical and essential role in the rejection of the intestine, using in vivo monoclonal antibody depletion studies. They will characterize the involvement of CD8 T cells in the rejection of the intestine and compare the role of CD8 cells in the intestine to heart transplant rejection. In the second observation, they have shown that mice genetically deficient in CD8 T cells retain the ability to reject intestine transplant. They will examine the mechanism by which treatment with anti-CD8 monoclonal antibodies prolong survival of intestinal allografts and contrast this to the mechanism used by CD8 knockout mice to reject similar grafts. Finally, they will take advantage of their model to study the unique role that CD8 T cells play in rejection in vivo. They will directly examine the costimulatory requirements and functional properties of CD8 T cells in mediating allograft rejection.