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

具有“直接”同种异体特异性的人类 Tregs 可以防止人源化小鼠模型中人类肝细胞的排斥反应。

• 批准号: G1002000/1
• 负责人: Niloufar Safinia
• 金额: $ 32.02万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1002000%2F1
• 关键词: Human; Tregs; direct; allospecificity; prevent

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.

肝移植是治疗严重肝病患者的一种成功方法。尽管如此，大多数患者终身维持免疫抑制剂（IS），伴随相关副作用，影响长期结局。因此，本研究的目的是设计方案，使患者能够接受移植物，而不需要长期使用IS。有趣的是，受体中的免疫细胞群，称为调节性T细胞，已被证明可以调节患者的免疫系统并防止器官排斥。我们研究的目的是开发新的治疗方法，包括增加受体中这些细胞的数量。我们将A。从受体中分离这些细胞，扩增它们并确保它们在培养中稳定。B.我们将确保它们对免疫系统具有“特异性”抑制作用，即它们防止肝脏排斥反应，但不会引起全面/全部免疫抑制。我们将使用肝移植的动物模型来证明这些细胞在重新引入患者体内之前的安全性和有效性。这项工作将为制定诱导耐受的方案铺平道路，从而实现更个性化的治疗，并最大限度地减少长期免疫抑制的并发症。