Targeting the complement system in transplantation

移植中针对补体系统

• 批准号: G0600892/1
• 负责人: Steven Sacks
• 金额: $ 163.07万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600892%2F1
• 关键词: Targeting; complement; system; transplantation

Complement consists of a normal set of circulating proteins whose role in fighting infection is long established, but which is also now known to impede the acceptance of healthy foreign tissue such as a kidney transplant. Complement seems to work together with more sophisticated elements of the immune response called T lymphocytes, and we now believe that collaboration between complement and T cells is essential for graft rejection. It follows that blocking the alliance between complement and lymphocytes may hold a key to a new method of treatment, which could lead to more effective prevention of graft rejection and allow lower use of toxic drugs that are directed against T lymphocytes. However in order to plan effectively, we need better understanding of the cells that produce and secrete complement and how complement enhances the performance of these cells to stimulate T lymphocytes. From a shortlist of two cell types transferred with the donor kidney, we propose to examine the relative importance of these cells types in triggering graft rejection. We also have strategies for reducing the secretion of complement by these cell types, and wish to see if we can build this into a treatment strategy suitable for clinical therapy. More effective ways to prevent rejection crises would be expected to cut graft losses in the short and long term, and thus lead to a significant health and economic benefit associated with transplant success.

补体由一组正常的循环蛋白质组成，其在对抗感染中的作用早已确立，但现在也知道它会阻碍健康的外来组织（如肾移植）的接受。补体似乎与称为T淋巴细胞的更复杂的免疫反应元件一起工作，我们现在相信补体和T细胞之间的合作对于移植物排斥至关重要。因此，阻断补体和淋巴细胞之间的联盟可能是一种新的治疗方法的关键，这可能会导致更有效地预防移植排斥反应，并减少针对T淋巴细胞的毒性药物的使用。然而，为了有效地计划，我们需要更好地了解产生和分泌补体的细胞以及补体如何增强这些细胞刺激T淋巴细胞的性能。从两种细胞类型的候选名单转移与供体肾，我们建议检查这些细胞类型在触发移植排斥反应的相对重要性。我们也有减少这些细胞类型的补体分泌的策略，并希望看看我们是否可以将其构建为适合临床治疗的治疗策略。更有效的方法来防止排斥危机将有望在短期和长期内减少移植损失，从而导致与移植成功相关的显著健康和经济效益。