在异体造血干细胞移植（allo-HSCT）中，调节免疫反应的方向是避免供体T细胞的反应不足和血液恶性肿瘤复发的关键，同时控制移植物抗宿主病（GVHD）的潜在发展，其中供体T细胞攻击受体组织。IL-2/抗IL-2复合物（IL2-Cxs）是一种选择性增强或减弱免疫反应的治疗选择。在专门的allo-HSCT实验模型中，包括将人细胞注射到免疫缺陷NSG小鼠中，我们同时评估了两种旨在增强调节性T细胞（Tregs）或激活效应性T细胞（Teffs）的IL-2Cxs对GVHD发生和肿瘤复发的治疗效果。我们还评估了复合物对体内免疫细胞表型和功能的影响。出乎意料的是，两种增强型Treg和Teff IL-2Cxs都能预防GVHD的发展。与未经处理的小鼠相比，它们都诱导了Treg的扩增并减少了CD8+ T细胞的数量。然而，只有接受增强型Treg IL-2Cx治疗的小鼠，显示出对衰竭的CD8+ T细胞的显著减少，符合强效抗肿瘤的效果。在人细胞上评估时，增强型Treg IL-2Cx在体外和体内均优先诱导Treg的扩增，同时在NSG小鼠中发展出强效的抗肿瘤效应。我们的结果证明了在HSCT后调节移植物抗反应性、促进GVL效应的临床相关性，使用增强型Treg而非增强型Teff IL2/抗IL-2复合物。

Modulating an immune response in opposite directions represents the holy grail in allogeneic hematopoietic stem cell transplantation (allo-HSCT) to avoid insufficient reactivity of donor T cells and hematologic malignancy relapse while controlling the potential development of graft-versus-host disease (GVHD), in which donor T cells attack the recipient's tissues. IL-2/anti-IL-2 complexes (IL2-Cxs) represents a therapeutic option to selectively accentuate or dampen the immune response. In dedicated experimental models of allo-HSCT, including also human cells injected in immunodeficient NSG mice, we evaluated side-by-side the therapeutic effect of two IL-2Cxs designed either to boost regulatory T cells (Tregs) or alternatively to activate effector T cells (Teffs), on GVHD occurrence and tumor relapse. We also evaluated the effect of the complexes on the phenotype and function of immune cells in vivo. Unexpectedly, both pro-Treg and pro-Teff IL-2Cxs prevented GVHD development. They both induced Treg expansion and reduced CD8+ T cells numbers, compared to untreated mice. However, only mice treated with the pro-Treg IL-2Cx, showed a dramatic reduction of exhausted CD8+ T cells, consistent with a potent anti-tumor effect. When evaluated on human cells, pro-Treg IL-2Cx also preferentially induced Treg expansion in vitro and in vivo, while allowing the development of a potent antitumor effect in NSG mice. Our results demonstrated the clinical relevance of using a pro-Treg, but not a pro-Teff IL2/anti-IL-2 complex to modulate alloreactivity after HSCT, while promoting a GVL effect.