导读：美国埃默里大学的研究人员利用小鼠移植模型，为异体造血干细胞移植中控制供体树突状细胞含量继而优化GVL和GVHD平衡提供了新的方法。为开发新的分离GVHD和GVL的策略提供了重要线索，具有重要的理论和实践意义。
来自美国埃默里大学的研究人员发表了题为“Interferon-gamma and indoleamine 2,3-dioxygenase signaling between donor dendritic cells and T cells regulates graft versus host and graft versus leukemia activity”的文章，利用小鼠移植模型，为异体造血干细胞移植中控制供体树突状细胞含量继而优化GVL和GVHD平衡提供了新的方法，相关成果公布在《血液》（Blood）杂志上。
文章的通讯作者是埃默里大学医学院Edmund K. Waller教授，第一作者是上海交通大学细胞分化与凋亡教育部重点实验室卢莹博士，卢莹博士曾荣获教育部优秀博士学位论文，近年来与Waller教授课题组合作，致力于移植物抗白血病（GVL）和GVHD活性的研究。
移植物抗宿主病（GVHD）是异基因骨髓移植的主要并发症和移植患者死亡的主要原因之一，开发安全有效和可行的抑制GVHD的方法是提高临床骨髓移植成功率所面临的迫切问题。
在这篇文章中，研究人员利用小鼠移植模型，发现注射供体浆细胞样树突状细胞可以显著提高小鼠的GVL效应，延长受体小鼠生存时间，同时抑制GVHD效应。进一步的机制研究发现，供体T细胞分泌的IFN-γ 和树突状细胞所产生的indoleamine 2,3-dioxygenase在抑制T细胞的免疫活性中发挥了关键作用。
这项研究为在异体造血干细胞移植中控制供体树突状细胞含量继而优化GVL 和GVHD平衡提供了新的方法，为开发新的分离GVHD和GVL的策略提供了重要线索，具有重要的理论和实践意义。
除此之外，近期第三军医大学的研究人员在处理造血干细胞移植并发症方面也获得了新发现，他们通过自主设计中西医四联药物组合方案预防肝静脉闭塞症及创建半相合造血干细胞移植后重度排斥反应防控的协同治疗手段，有效降低了白血病移植后主要致死性并发症问题，使得不全相合造血干细胞移植后急慢性排斥反应发生率大幅下降，达到了同胞间全相合造血干细胞移植后防控水平，保障了高难度造血干细胞移植的顺利开展。目前，该技术国内外均未见文献报道。
Interferon-gamma and indoleamine 2,3-dioxygenase signaling between donor dendritic cells and T cells regulates graft versus host and graft versus leukemia activity
Ying Lu, Cynthia R. Giver, Akshay Sharma, Jian Ming Li, Katarzyna A. Darlak, Lauren M. Owens, John D. Roback, Jacques Galipeau, and Edmund K. Waller
Allogeneic hematopoietic stem cell transplantation (HSCT) can eradicate chemo-refractory leukemia through the graft-versus-leukemia (GvL) activity of donor T-cells. However, the clinical success of allo-HSCT is limited by the graft-versus-host disease (GvHD) activity of donor T-cells. We have previously reported that donor bone marrow precursors of plasmacytoid dendritic cells (pre-pDC) can activate donor T-cells towards Th1 immune polarization in murine allogeneic HSCT. To optimize the GvL activity of these activated donor T-cells and limit their GvH activity, we engineered the cellular constituents of an allogeneic hematopoietic stem cell graft with highly purified hematopoietic stem cells, T-cells and pre-pDC and studied their GvL and GvHD activities in a murine model of allogeneic HSCT. Transplanted donor pre-pDC expanded in vivo for two weeks post-transplant, and markedly augmented the activation and GvL activity of donor T-cells while attenuating their GvHD activity, leading to an improved therapeutic index. Bi-directional signaling between donor T-cells and donor pDC with interferon-γ synthesis by donor T-cells inducing indoleamine 2,3-dioxygenase (IDO) synthesis by donor pDC limited GvHD by altering the balance between donor T-reg and inflammatory T-cells. Manipulating the content of donor dendritic cell precursors in allogeneic HSCT is a novel method to optimize the balance between GvL and GvHD.
