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

Frontiers in Immunology

Yuan Song¹  Ying Zhu¹  Yonghao Liu¹  Haiyan Liu¹  Chen Dong²  Dandan Lin³  Ziqi Jin³  Depei Wu³  Bo Hu³  Zhinan Yin⁴ 

[1] Immunology Programme, Life Sciences Institute and Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore;Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China;Institute of Blood and Marrow Transplantation, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Collaborative Innovation Center of Hematology, National Clinical Research Center for Hematologic Diseases, Soochow University, Suzhou, China;The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou, China;Zhuhai Precision Medical Center, Zhuhai People’s Hospital (Zhuhai Hospital Affiliated With Jinan University), Jinan University, Zhuhai, China;

关键词: γδT cells;    IL-17;    graft-versus-host disease;    graft-versus-leukemia;    hematopoietic stem cell transplantation;   

DOI  :  10.3389/fimmu.2020.558143

来源: DOAJ

【 摘 要 】

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 αβT cells are extensively studied, the role of donor γδT cells in allo-HSCT is less well defined. Using TCRδ-/- donors lacking γδT cells, we demonstrated that donor γδT cells were critical in mediating graft-versus-leukemia (GVL) effect during allo-HSCT. In the absence of donor γδT cells, IFN-γ production by CD8+ T cells was severely impaired. Vγ4 subset was the major γδT cell subset mediating the GVL effect in vivo, which was partially dependent on IL-17A. Meanwhile, donor γδT cells could mitigate acute GVHD in a murine allo-HSCT model by suppressing CD4+ T cell activation and the major γδT cell subset that exerted this protective function was also Vγ4 γδT cells. Therefore, our findings provide evidence that donor γδT cells, especially Vγ4 subset, can enhance GVL effect and mitigate aGVHD during allo-HSCT.

【 授权许可】

Unknown