Graft-versus-host disease (GVHD) is the main complication after allogeneic hematopoietic stem cell transplantation. We previously unveiled a correlation between proportions of C-C motif chemokine receptor 7 (CCR7)⁺ T cells in the apheresis and the risk of developing GVHD. We wanted to evaluate in vivo whether apheresis with low proportion of CCR7⁺ cells or treatment with an anti-human CCR7 monoclonal antibody (mAb) were suitable strategies to prevent or treat acute GVHD in preclinical xenogeneic models. Therapeutic anti-CCR7 mAb was the most effective strategy in both prophylactic and therapeutic settings where antibody drastically reduced in vivo lymphoid organ infiltration of donor CCR7⁺ T cells, extended lifespan and solved clinical signs. The antibody neutralized in vitro migration of naïve and central memory T cells toward CCR7 ligands and depleted target CCR7⁺ subsets through complement activation. Both mechanisms of action spared CCR7⁻ subsets, including effector memory and effector memory CD45RA⁺ T cells which may mediate graft versus leukemia effect and immunity against infections. Accordingly, the numbers of donor CCR7⁺ T cells in the apheresis were not associated to cytomegalovirus reactivation or the recurrence of the underlying disease. These findings provide a promising new strategy to prevent and treat acute GVHD, a condition where new specific, safety and effective treatment is needed.

移植物抗宿主病（GVHD）是异基因造血干细胞移植后的主要并发症。我们之前揭示了单采术中 CC 基序趋化因子受体 7 (CCR7) ⁺ T 细胞的比例与发生 GVHD 的风险之间的相关性。我们想在体内评估低比例 CCR7 ⁺细胞的单采术或用抗人 CCR7 单克隆抗体 (mAb) 治疗是否是预防或治疗临床前异种模型中急性 GVHD 的合适策略。治疗性抗 CCR7 mAb 是预防和治疗环境中最有效的策略，其中抗体显着减少供体 CCR7 的体内淋巴器官浸润⁺T 细胞，延长寿命并解决临床症状。该抗体中和了幼稚和中央记忆 T 细胞向 CCR7 配体的体外迁移，并通过补体激活耗尽了目标 CCR7 ⁺亚群。两种作用机制都避免了 CCR7 ^-亚群，包括效应记忆和效应记忆 CD45RA ⁺  T 细胞，它们可能介导移植物抗白血病效应和抗感染免疫。因此，单采中供体 CCR7 ⁺ T 细胞的数量与巨细胞病毒再激活或潜在疾病的复发无关。这些发现为预防和治疗急性 GVHD 提供了一种有希望的新策略，这种情况需要新的特异性、安全和有效的治疗方法。