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

点击翻译按钮获取中文摘要

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.