The role of T-cell apoptosis in transplantation tolerance

器官移植是晚期心脏、肺、肝或肾衰竭患者的治疗选择，这些手术的早期成功率有了惊人的提高。然而，10年移植物存活率在过去15年中没有太大变化。克服这个问题的一种方法是操纵免疫系统，使移植被无限期地接受。这被称为耐受性，它通过在短时间内给予强烈的免疫抑制来起作用，以便移植物被无限期地接受，而不需要长期的免疫抑制。导致这种现象的免疫机制很复杂，人们对其了解甚少。该项目旨在研究免疫系统中导致移植耐受的早期事件。特别地，将研究涉及白色血细胞中的程序性细胞死亡的因素。将使用在细胞死亡机制中具有阻断的专门饲养的小鼠来确定这些阻断对诱导耐受性的能力具有什么影响。其他经过基因改造的老鼠，其白色细胞将被用来研究这些细胞的命运。如果能更好地理解诱导耐受的机制，那么就有可能设计出特异性的免疫抑制药物，用于在移植患者中产生耐受。

Organ transplantation is the treatment of choice for patients with end-stage heart, lung, liver or kidney failure and there have been spectacular improvements in the early success of these procedures. However the 10 year graft survival rate has not changed much in the past 15 years. One way of overcoming this problem is to manipulate the immune system so that the transplant is accepted indefinitely. This is called tolerance and it works by giving intense immunosuppression for a short period so that the transplant is accepted indefinitely without the need for long term immunosuppression. The immune mechanism responsible for this phenomenon is complex and is poorly understood. This project aims to study the early events in the immune system that leads to transplantation tolerance. In particular, factors involved in programmed cell death in white blood cells will be studied. Specially bred mice that have blocks in the cell death mechanisms will used to determine what effects these blocks have on the ability to induce tolerance. Other mice that have been genetically altered to allow their white cells to be tracked will be used to study the fate of these cells. If the mechanisms involved in tolerance induction are better understood, then it will be possible to design specific immunosuppressive drugs that will be used to produce tolerance in transplant patients.