Receptors for C3a and C5a modify dendritic cell function in alloreactive T cell responses and allograft rejection

对细菌和病毒等入侵生物的防御始于即刻的炎症反应，几天后是由被称为T淋巴细胞的白细胞提供的更持久的免疫。在先天炎症反应的帮助下，T淋巴细胞清除入侵的生物体的方式大致相同，这些防御机制识别为来自无关捐赠者的外来器官移植，导致捐赠者的排斥反应。通过研究称为补体的炎症反应的蛋白质，我们实验室和其他中心的工作已经表明，T淋巴细胞只有在补体存在的情况下才能正常发挥作用；没有补体的移植肾可以存活更长时间。我们的目标是了解补体如何驱动免疫反应，并开发防止补体致病的治疗方法。我们认为补体通过一种中间类型的细胞(树突状细胞)作用于免疫系统，该细胞将指令传递给静止的T淋巴细胞，提醒它们注意异物的存在。我们将仔细检查树突状细胞检测激活补体片段的能力，并检查阻断树突状细胞感知补体激活的能力是否会削弱免疫系统产生有害T细胞的能力，从而降低移植排斥反应的风险。如果我们成功地展示了补体如何刺激有害的T细胞，这可能会提供一个有价值的手段来阻止器官移植的免疫反应，从而防止排斥反应。

Defence against invasive organisms such as bacteria and viruses begins with an immediate inflammatory response, which is followed a few days later by more lasting immunity provided by white cells known as T lymphocytes. In much the same way that T lymphocytes, with the help of the innate inflammatory response, eliminates invading organisms, these defences recognise as foreign, organ transplants from an unrelated donor, leading to rejection of the donor organ. By studying proteins of the inflammatory response called complement, work in our laboratory and at other centres has already shown that T lymphocytes can only function properly in the presence of complement; without complement transplanted kidney survives for much longer. Our aim is to learn how complement drives the immune response and to develop treatments that prevent complement from causing disease. We believe that complement acts on the immune system through an intermediary type of cell (dendritic cell) that passes on instructions to resting T lymphocytes alerting them to the presence of foreign material. We will carefully examine the ability of dendritic cells to detect activated complement fragments and examine whether blockade of this ability of dendritic cells to sense complement activation will blunt the capacity of the immune system to generate harmful T cells, and thus reduce the risk of transplant rejection. If we are successful in showing how complement stimulates harmful T cells, this may offer a valuable means to block the immune response against organ transplants and thus prevent rejection.