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

异基因造血干细胞移植是指将造血干细胞（或骨髓）从健康供体转移到患者体内。这种手术可以治愈患有许多其他方法无法治愈的疾病的患者，包括患有白血病等血液癌症的患者。然而，限制同种异体干细胞移植成功的主要问题是移植物抗宿主病，这是移植物中包含的供体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不能令人满意，因为它们抑制了所有免疫细胞的恢复，导致移植后感染和癌症复发增加。我们最近发现了一种在同种异体移植前操纵人类供体细胞的方法，该方法导致产生可以抑制移植物抗宿主病反应的免疫细胞。该项目的目的是在实验室中开发方法来改进该技术，以提供可用于预防移植物抗宿主病的供体免疫细胞，而不会影响同种异体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同种异体移植后的移植物抗宿主病，使其成为一种更安全，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.