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<p>Immune homeostasis is a dynamic equilibrium between immunogenicity and immune tolerance, essential for maintaining overall health. This balance relies on the immune system’s ability to distinguish between self and non-self antigens, a process governed by human leukocyte antigens (HLAs). While self-versus-non-self recognition serves as a crucial immunological barrier against foreign antigens in steady state, it also drives bidirectional alloreactivity in allogeneic hematopoietic stem cell transplantation (allo-HSCT). HLA mismatches in haploidentical HSCT (haplo-HSCT) pose significant challenges, increasing the risk of life-threatening graft-versus-host disease (GVHD) and graft rejection, historically leading to poor outcomes. However, over the past two decades, substantial advancements have optimized haplo-SCT, achieving outcomes comparable with those of HLA-matched HSCT. By successfully overcoming the HLA barrier, haplo-HSCT provides a unique opportunity to investigate the underlying cellular and molecular fundamentals governing immune homeostasis restoration following allo-HSCT. In this review, we discuss the foundation of immune homeostasis in steady state and its remodeling after allo-HSCT.</p>

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HLA haploidentical HSCT: from immune imbalance to a platform for immune homeostasis restoration

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月4日

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  • Huidong Guo,
  • Zheng-Li Xu,
  • Xu-Ying Pei,
  • Xiang-Yu Zhao,
  • Xiao-Jun Huang

摘要

Immune homeostasis is a dynamic equilibrium between immunogenicity and immune tolerance, essential for maintaining overall health. This balance relies on the immune system’s ability to distinguish between self and non-self antigens, a process governed by human leukocyte antigens (HLAs). While self-versus-non-self recognition serves as a crucial immunological barrier against foreign antigens in steady state, it also drives bidirectional alloreactivity in allogeneic hematopoietic stem cell transplantation (allo-HSCT). HLA mismatches in haploidentical HSCT (haplo-HSCT) pose significant challenges, increasing the risk of life-threatening graft-versus-host disease (GVHD) and graft rejection, historically leading to poor outcomes. However, over the past two decades, substantial advancements have optimized haplo-SCT, achieving outcomes comparable with those of HLA-matched HSCT. By successfully overcoming the HLA barrier, haplo-HSCT provides a unique opportunity to investigate the underlying cellular and molecular fundamentals governing immune homeostasis restoration following allo-HSCT. In this review, we discuss the foundation of immune homeostasis in steady state and its remodeling after allo-HSCT.