Generation of suppressive donor T cells to specifically control alloresponses after allogeneic stem cell transplantation

异基因干细胞移植包括将健康捐赠者的血液干细胞(或骨髓)移植到患者身上。这种手术可以治愈许多原本无法治愈的疾病，包括白血病等血癌患者。然而，限制异基因干细胞移植成功的一个主要问题是移植物抗宿主病，即移植体内包含的供者免疫细胞对健康患者组织的破坏。目前预防移植物抗宿主病的技术并不令人满意，因为它们抑制了所有免疫细胞的恢复，导致移植后感染增加和癌症复发。我们最近发现了一种在异基因移植前操纵人类供体细胞的方法，这种方法可以产生免疫细胞，从而抑制移植物抗宿主疾病反应。该项目的目的是在实验室开发改进这项技术的方法，以提供供体免疫细胞，这些细胞可用于预防移植物抗宿主疾病，而不影响异基因移植后免疫系统的健康恢复。我们希望这可能会导致一种更好的方法来预防异基因移植后的移植物抗宿主病，使其成为一种更安全和更有效的治疗方法。

Allogeneic stem cell transplantation consists of the transfer of blood stem cells (or bone marrow) from a healthy donor to a patient. This procedure can cure patients with many diseases that would be otherwise incurable, including those with cancers of the blood such as leukaemia. However, a major problem that limits the success of allogeneic stem cell transplantation is graft-versus-host disease, which is the destruction of healthy patient tissues by donor immune cells contained within the transplant. Current techniques to prevent graft-versus-host disease are unsatisfactory as they suppress the recovery of all immune cells, resulting in increased infection and cancer relapse after transplant. We have recently identified a way of manipulating human donor cells before allogeneic transplantation that leads to the production of immune cells which can suppress graft-versus-host disease responses. The aim of this project is to develop ways in the laboratory to improve this technique to provide donor immune cells which could be used to prevent graft-versus-host disease without affecting the healthy recovery of the immune system after allogeneic transplantation. We hope that this might lead to a better way to prevent graft-versus-host disease after allogeneic transplantation, making this a safer and more effective treatment.