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

Abstract

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 ??T cells are extensively studied, the role of donor ??T cells in allo-HSCT is less well defined. Using TCR?-/- donors lacking ??T cells, we demonstrated that donor ??T cells were critical in mediating graft-versus-leukemia (GVL) effect during allo-HSCT. In the absence of donor ??T cells, IFN-? production by CD8+ T cells was severely impaired. V?4 subset was the major ??T cell subset mediating the GVL effect in vivo, which was partially dependent on IL-17A. Meanwhile, donor ??T cells could mitigate acute GVHD in a murine allo-HSCT model by suppressing CD4+ T cell activation and the major ??T cell subset that exerted this protective function was also V?4 ??T cells. Therefore, our findings provide evidence that donor ??T cells, especially V?4 subset, can enhance GVL effect and mitigate aGVHD during allo-HSCT. © Copyright © 2020 Song, Zhu, Hu, Liu, Lin, Jin, Yin, Dong, Wu and Liu.