Targeting the complement system in transplantation

补体由一组正常的循环蛋白组成，它们在抵抗感染方面的作用早已确立，但现在已知它也会阻碍对健康的外来组织的接受，如肾脏移植。补体似乎与免疫反应中更复杂的T淋巴细胞一起工作，我们现在认为补体和T细胞之间的合作是移植排斥反应的关键。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，这种方法可能会导致更有效地预防移植物排斥反应，并允许针对T淋巴细胞的有毒药物的使用减少。然而，为了有效地进行计划，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。从与供体肾移植的两种细胞类型的入围名单中，我们建议检查这些细胞类型在触发移植排斥反应中的相对重要性。我们也有减少这些类型细胞分泌补体的策略，并希望看看是否可以将其构建为适合临床治疗的治疗策略。更有效的预防排斥危机的方法有望在短期和长期内减少移植物的损失，从而带来与移植成功相关的显著的健康和经济利益。

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.