Donor γδT Cells Promote GVL Effect and Mitigate aGVHD in Allogeneic Hematopoietic Stem Cell Transplantation

Disease relapse and graft-versus-host disease (GVHD) are the major complications affecting the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). While the functions of alpha beta T cells are extensively studied, the role of donor gamma delta T cells in allo-HSCT is less well defined. Using TCR delta(-/-) donors lacking gamma delta T cells, we demonstrated that donor gamma delta T cells were critical in mediating graft-versus-leukemia (GVL) effect during allo-HSCT. In the absence of donor gamma delta T cells, IFN-gamma production by CD8(+) T cells was severely impaired. V gamma 4 subset was the major gamma delta T cell subset mediating the GVL effect in vivo, which was partially dependent on IL-17A. Meanwhile, donor gamma delta T cells could mitigate acute GVHD in a murine allo-HSCT model by suppressing CD4(+) T cell activation and the major gamma delta T cell subset that exerted this protective function was also V gamma 4 gamma delta T cells. Therefore, our findings provide evidence that donor gamma delta T cells, especially V gamma 4 subset, can enhance GVL effect and mitigate aGVHD during allo-HSCT.