〔Abstract〕 Objective 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 histocompatibility antigen-specific donor central memory T cells (miHA-TM) combined with a CD40 agonist were adoptively 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 immune 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 promoted donor bone marrow engraftment. ConclusionmiHA-TM facilitates immune reconstitution in recipients without inducing graft-versus-host disease.