γδ (γδ) T 细胞只占人类 T 细胞库的一小部分，但在同种异体造血干细胞移植 (allo-HSCT) 的背景下，在介导抗感染和抗肿瘤作用方面发挥着重要作用。我们进行了一项前瞻性研究来分析不同移植方式对 γδ T 细胞及其亚群免疫重建的影响。并行分析 CD3、CD4 和 CD8 T 细胞。其次，我们研究了 γδ T 细胞重建对临床结果的影响，包括急性移植物抗宿主病 (aGvHD) 和病毒感染。我们的队列包括 49 名儿科患者，他们接受了来自匹配的无关 (MUD) 或匹配的相关 (MRD) 捐赠者的未经操作的骨髓移植。该队列包括患有恶性和非恶性疾病的患者。在移植后15、30、60、100、180和240天使用流式细胞术测量细胞计数。对细胞进行 CD3、CD4、CD8、CD45、TCRαβ、TCRγδ、TCRVδ1、TCRVδ2、HLA-DR 及其组合染色。在单变量分析中，在时间点 30、60、100（分别为 p<0.001）和 180（p<0.01）时，MRD 患者的 Vδ2 T 细胞显着高于 MUD 患者。这些结果在多变量分析中仍然显着。总 γδ T 细胞和 Vδ2 T 细胞相对丰度恢复的患者移植后 II-IV 级 aGvHD 累积发生率显着降低（分别为 p=0.03 和 p=0.04）。 Vδ2 T 细胞相对丰度较高也与 EBV 感染发生率较低相关（p=0.02）。另一方面，与未感染 EBV 的患者相比，感染 EBV 的患者在移植后第 100 天和 180 天表现出更高的绝对 Vδ1 T 细胞计数（分别为 p=0.046 和 0.038）。该结果在多变量时间平均分析中仍然显着（q<0.1）。我们的结果表明，γδ T 细胞，尤其是 Vδ2 T 细胞亚群对儿科 HSCT 后 aGvHD 和 EBV 感染的发展具有保护作用。 Vδ1 T 细胞可能参与 EBV 感染后的免疫反应。我们的结果鼓励进一步研究 γδ T 细胞作为 HSCT 后的预后标志物以及过继性 T 细胞转移策略的可能靶标。版权所有 © 2024 Müller、Alasfar、Preuß、Zimmermann、Streitz、Hundsdörfer、Eggert、Schulte、von Stackelberg 和 Oevermann。

Gamma delta (γδ) T cells represent a minor fraction of human T cell repertoire but play an important role in mediating anti-infectious and anti-tumorous effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a prospective study to analyze the effect of different transplant modalities on immune reconstitution of γδ T cells and subsets. CD3, CD4 and CD8 T cells were analyzed in parallel. Secondly, we examined the impact of γδ T cell reconstitution on clinical outcomes including acute Graft-versus-Host-Disease (aGvHD) and viral infections. Our cohort includes 49 pediatric patients who received unmanipulated bone marrow grafts from matched unrelated (MUD) or matched related (MRD) donors. The cohort includes patients with malignant as well as non-malignant diseases. Cell counts were measured using flow cytometry at 15, 30, 60, 100, 180 and 240 days after transplantation. Cells were stained for CD3, CD4, CD8, CD45, TCRαβ, TCRγδ, TCRVδ1, TCRVδ2, HLA-DR and combinations. Patients with a MRD showed significantly higher Vδ2+ T cells than those with MUD at timepoints +30, +60, +100 (p<0.001, respectively) and +180 (p<0.01) in univariate analysis. These results remained significant in multivariate analysis. Patients recovering with a high relative abundance of total γδ T cells and Vδ2+ T cells had a significantly lower cumulative incidence of grade II-IV aGvHD after transplantation (p=0.03 and p=0.04, respectively). A high relative abundance of Vδ2+ T cells was also associated with a lower incidence of EBV infection (p=0.02). Patients with EBV infection on the other hand showed higher absolute Vδ1+ T cell counts at days +100 and +180 after transplantation (p=0.046 and 0.038, respectively) than those without EBV infection. This result remained significant in a multivariate time-averaged analysis (q<0.1). Our results suggest a protective role of γδ T cells and especially Vδ2+ T cell subset against the development of aGvHD and EBV infection after pediatric HSCT. Vδ1+ T cells might be involved in the immune response after EBV infection. Our results encourage further research on γδ T cells as prognostic markers after HSCT and as possible targets of adoptive T cell transfer strategies.Copyright © 2024 Müller, Alasfar, Preuß, Zimmermann, Streitz, Hundsdörfer, Eggert, Schulte, von Stackelberg and Oevermann.