ANTIBODY RESPONSE IN HUMANS TO PIG XENOANTIGENS

人体器官捐献者的短缺是一个关键的限制， 移植广泛用于治疗严重疾病。 使用非人类物种，特别是猪，作为器官捐赠者 为解决捐献器官短缺问题提供了一个可能的解决方案。 使用 其他物种的组织（异种移植物）在很大程度上是不成功的 由于缺乏对宿主免疫系统的了解， 对异种移植物的反应和当前免疫抑制剂的失败 移植物长期存活的技术。 的早期阶段 异种移植排斥反应以体液免疫为主 响应和本申请中提出的实验设计 为了更全面地了解主机的这一组成部分， 反应 我们打算确定控制免疫球蛋白基因， 暴露于猪组织、分离株的患者产生的抗体应答 并表征具有功能能力的人抗体， 介导猪异种移植物的排斥反应，并鉴定特异性亚群 产生这些抗体的B淋巴细胞。 我们以前的 在啮齿类动物中的实验工作已经证明了异种移植反应 似乎是一种独特的T细胞非依赖性抗体产生形式 由一组密切相关的IG基因控制。 我们提出 这种类型的免疫反应是一个共同的特点， 异种移植反应，即使是不同的物种组合， 本提案中概述的实验旨在扩展这些 研究，以检查人对猪的抗体反应 异种移植 我们相信如果有一小部分 免疫球蛋白基因负责控制体液免疫 异种移植物在患者中的反应，这些信息可以提供 制定新的预防战略的基础 反应

The shortage of human organ donors is a critical limitation in the widespread use of transplantation as a treatment for serious diseases. The use of non-human species, particularly the pig, as organ donors offers a potential solution to this shortage of donor organs. The use of tissues from other species (xenografts) has largely been unsuccessful because of a lack of understanding of the nature of the host's immune response to xenografts and the failure of current immunosuppressive techniques to allow for long-term graft survival. The early phases of the xenograft rejection reaction are dominated by humoral immune responses and the experiments proposed in this application are designed to establish a more complete understanding of this component of the host response. We intend identify the immunoglobulin genes that control the antibody response(s) mounted by patients exposed to pig tissues, isolate and characterize human antibodies that have the functional capacity to mediate rejection of pig xenografts, and identify the specific subsets of B lymphocytes that produce these antibodies. Our previous experimental work in rodents has demonstrated the xenograft response appears to be a unique form of T cell-independent antibody production controlled by a closely-related group of Ig genes. We have proposed that this type of immune response is a common feature of the early xenograft reaction, even for diverse species combinations, and the experiments outlined in this proposal are intended to extend these studies to an examination of the human antibody response to pig xenografts. We believe if a small group of closely-related immunoglobulin genes are responsible for controlling the humoral response of xenografts in patients, this information may provide the basis for the development of new strategies for preventing this reaction.