2020年10月，吴德沛教授、刘海燕教授课题组在《Frontiers inImmunology》杂志发表最新研究成果“DonorγδT Cells Promote GVL Effect and Mitigate aGVHD in Allogeneic HematopoieticStem Cell Transplantation”。该研究证明在异基因造血干细胞移植中，供者γδT细胞，尤其是供者Vγ4γδT细胞亚群能够在促进移植物抗白血病复发效应的同时，显著减轻移植物抗宿主病作用。

根据TCR类型，T细胞可以分为表达TCRαβ的αβT细胞和表达TCRγδ的γδT细胞。在异基因造血干细胞移植（allo-HSCT）中，供者αβT细胞被认为是发挥移植物抗白血病（GVL）效应和造成移植物抗宿主病（GVHD）的主要T细胞群体，然而供者γδT细胞在allo-HSCT中的作用及机制却尚不明确。课题组利用TCRδ^-/-小鼠作为供体鼠构建GVL小鼠模型，发现供者γδT细胞在GVL效应中发挥重要作用，供者γδT细胞的缺失显著减少CD8⁺T细胞IFN-γ的表达。供者Vγ1γδT细胞亚群及Vγ4γδT细胞亚群抗体清除及过继性回输实验进一步显示供者Vγ4γδT细胞亚群是发挥促GVL效应的主要γδT细胞群体。课题组利用野生型供体鼠或IL-17A^-/-供体鼠培养获得Vγ4γδT细胞并进行过继性回输，发现供者Vγ4γδT细胞的促GVL效应部分依赖于其表达的IL-17A。在小鼠急性GVHD（aGVHD）模型中，课题组发现供者γδT细胞的缺失显著促进供者CD4⁺T细胞的激活进而加重aGVHD病情，有趣的是，过继性回输实验表明在aGVHD中发挥该免疫调控作用的主要亚群仍是Vγ4γδT细胞。以上研究结果表明供者γδT细胞，尤其是Vγ4γδT细胞亚群在allo-HSCT中能够兼顾促进GVL效应及减轻aGVHD病情的重要免疫调控作用。

原文摘要：Diseaserelapse and graft-versus-host disease (GVHD) are the major complications affectingthe outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT).While the functions of αβT cells are extensively studied, the role of donor gdTcells in allo-HSCT is less well defined. Using TCRδ^-/-donorslacking γδT cells, we demonstrated that donor γδT cells were critical inmediating graft-versus-leukemia (GVL) effect during allo-HSCT. In the absenceof donor γδT cells, IFN-γ production by CD8⁺T cells was severelyimpaired. Vγ4 subset was the major γδT cell subset mediating the GVL effectin vivo, which was partially dependenton IL-17A. Meanwhile, donor γδT cells could mitigate acute GVHD in a murineallo-HSCT model by suppressing CD4⁺T cell activation and the major γδTcell subset that exerted this protective function was also Vγ4γδT cells.Therefore, our findings provide evidence that donor γδT cells, especially Vγ4 subset,can enhance GVL effect and mitigate aGVHD during allo-HSCT.