Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA, United States.
Department of Medicine, Pennsylvania State University, Hershey, PA, United States.
Front Immunol. 2019 Feb 1;10:93. doi: 10.3389/fimmu.2019.00093. eCollection 2019.
Graft-vs.-host disease (GVHD) remains a significant cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Significant progresses have been made in defining the dichotomous role of dendritic cells (DCs) in the development of GVHD. Host-derived DCs are important to elicit allogeneic T cell responses, whereas certain donor-types of DCs derived from newly engrafted hematopoietic stem/progenitor cells (HSPCs) can amply this graft-vs.-host reaction. In contrast, some DCs also play non-redundant roles in mediating immune tolerance. They induce apoptotic deletion of host-reactive donor T cells while promoting expansion and function of regulatory T cells (Treg). Unfortunately, this tolerogenic effect of DCs is impaired during GVHD. Severe GVHD in patients subject to allo-HSCT is associated with significantly decreased number of circulating peripheral blood DCs during engraftment. Existing studies reveal that GVHD causes delayed reconstitution of donor DCs from engrafted HSPCs, impairs the antigen presentation function of newly generated DCs and reduces the capacity of DCs to regulate Treg. The present review will discuss the importance of DCs in alloimmunity and the mechanism underlying DC reconstitution after allo-HSCT.
移植物抗宿主病（GVHD）仍然是异基因造血干细胞移植（allo-HSCT）后发病率和死亡率的重要原因。在确定树突状细胞（DCs）在 GVHD 发展中的双重作用方面已经取得了重大进展。宿主来源的 DCs 对于引发同种异体 T 细胞反应很重要，而来自新植入造血干细胞/祖细胞（HSPCs）的某些供体类型的 DCs 可以充分放大这种移植物抗宿主反应。相比之下，某些 DCs 也在介导免疫耐受方面发挥非冗余作用。它们诱导宿主反应性供体 T 细胞的凋亡性删除，同时促进调节性 T 细胞（Treg）的扩增和功能。不幸的是，DCs 的这种耐受作用在 GVHD 期间受损。接受 allo-HSCT 的患者发生严重 GVHD 与植入期间外周血循环 DC 数量明显减少有关。现有研究表明，GVHD 导致来自植入 HSPC 的供体 DC 重建延迟，损害新生成的 DC 的抗原呈递功能，并降低 DC 调节 Treg 的能力。本综述将讨论 DCs 在同种免疫中的重要性以及 allo-HSCT 后 DC 重建的机制。
