Human Tregs with 'direct' allospecificity can prevent rejection of human hepatocytes in a humanised mouse model.

肝移植是治疗严重肝病的一种成功方法。尽管如此，大多数患者仍然长期服用免疫抑制剂(IS)，并伴随着相关的副作用，影响长期结果。因此，这项研究的目标是设计方案，使患者能够接受他们的移植物，而不需要长期使用IS。有趣的是，受体中的免疫细胞群被称为调节性T细胞，已被证明可以调节患者的免疫系统，防止器官排斥。我们研究的目的是开发新的治疗方法，包括增加受者体内这些细胞的数量。我们将A.将这些细胞从受体中分离出来，进行扩增，并确保它们在培养中稳定。B.我们将确保它们在免疫系统中具有“特定的”抑制作用，即它们防止肝脏排斥反应，但不会导致全身/全部免疫抑制。c.在重新引入患者之前，我们将使用肝移植的动物模型来证明这些细胞的安全性和有效性。这项工作将为制定诱导耐受的方案铺平道路，导致更个体化的治疗，并将长期免疫抑制的并发症降至最低。

Liver transplantation is a successful treatment for patients with severe liver disease. Despite this, the majority of patients are maintained on immunosuppressants (IS) life long with associated side effects, affecting long term outcome. The goal of this study is, therefore, to devise protocols to enable the patient to accept their graft without the need for long term use of IS. Interestingly, populations of immune cells in the recipient, called regulatory T cells, have been shown to regulate the patient‘s immune system and prevent against organ rejection. The aim of our research is to develop new treatments that involve increasing the number of these cells in the recipient. We will a. isolate these cells from the recipient, expand them and ensure they are stable in culture. b. we will ensure they have a ‘specific‘ inhibitory role on the immune system i.e. they prevent liver rejection, but do not cause general/total immunosuppression c. We will use animal models of liver transplantation to show the safety and efficacy of these cells before re-introduction into the patient. This work will pave the way towards the development of protocols to induce tolerance, leading to more individualized treatment and minimize the complications of long term immunosuppression.