T Cell immune reconstitution after allo-HSCT: key factors and implications

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a curative therapy for hematological malignancies, with T-cell immune reconstitution playing a pivotal role in determining clinical outcomes. This review comprehensively illustrates the processes and influencing factors of T-cell recovery post-HSCT, highlighting the dual pathways of reconstitution: thymus-independent peripheral expansion and thymus-dependent central regeneration. Key factors such as recipient and donor age, human leukocyte antigen disparity, conditioning regimens, immunosuppressive therapies, cytomegalovirus reactivation, and graft-versus-host disease (GVHD) significantly impact T-cell reconstitution dynamics and functional recovery. Furthermore, the article discusses the critical balance between graft-versus-leukemia (GVL) effects and GVHD, emphasizing how T-cell exhaustion, inhibitory receptor overexpression, and clonal dynamics contribute to relapse. Emerging technologies, including single-cell multi-omics, spatially resolved proteomics, T cell receptor repertoire analysis, and artificial intelligence-driven modeling, are explored for their potential to deepen mechanistic understanding and enable personalized therapeutic strategies. Ultimately, enhancing T-cell reconstitution through optimized transplantation protocols and targeted interventions is essential for reducing complications and improving long-term survival.