〔Abstract〕 To treat malignant and non-malignant hematological diseases , allogeneic hematopoietic stem cell transplantation (alloSCT) is widely used . However , its application is limited by the risk of graft-versus-host disease (GVHD) , difficulties in donor matching , and the high incidence of transplantation-related mortality due to myeloablative conditioning regimens . Therefore , there is an urgent need to develop new strategies that reduce the intensity of conditioning while enhancing donor engraftment efficiency. Methods In an alloSCT model , minor his- tocompatibility antigen-specific donor central memory T cells ( miHA-TM) combined with a CD40 agonist were a- doptively transferred to evaluate donor bone marrow engraftment under different irradiation doses . Results Minor histocompatibility antigen ( miHA)-specific donor-derived central memory T cells ( TM) facilitated recipient im- mune reconstitution without inducing GVHD . Donor-derived TM cells , however , underwent exhaustion during the process of recipient immune reconstitution , which compromised complete donor engraftment under reduced-intensity conditioning . At a low irradiation dose (4 Gy) , the combination of miHA-TM and a CD40 agonist significantly pro- moted donor bone marrow engraftment. Conclusion miHA-TM facilitates immune reconstitution in recipients without inducing graft-versus-host disease .