Department of Pediatric Oncology and Hematology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Department of Internal Medicine V: Hematology, Oncology and Rheumatology, University Hospital Heidelberg, Heidelberg, Germany.
Front Immunol. 2024 Jul 29;15:1433785. doi: 10.3389/fimmu.2024.1433785. eCollection 2024.
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, TCR, 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.
γδ（γδ）T 细胞在同种异体造血干细胞移植（allo-HSCT）背景下介导抗感染和抗肿瘤作用中代表人类 T 细胞库的一小部分，但起着重要作用。我们进行了一项前瞻性研究，以分析不同移植方式对γδ T 细胞和亚群免疫重建的影响。同时分析 CD3、CD4 和 CD8 T 细胞。其次，我们研究了γδ T 细胞重建对包括急性移植物抗宿主病（aGvHD）和病毒感染在内的临床结果的影响。我们的队列包括 49 名接受未修饰的骨髓移植物来自匹配的无关（MUD）或匹配的相关（MRD）供体的儿科患者。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 天时，使用流式细胞术测量细胞计数。细胞用 CD3、CD4、CD8、CD45、TCR、TCRγδ、TCRVδ1、TCRVδ2、HLA-DR 和组合进行染色。在单变量分析中，MRD 患者在 +30、+60、+100（p<0.001）和 +180（p<0.01）时显示出比 MUD 患者显著更高的 Vδ2+T 细胞。这些结果在多变量分析中仍然具有统计学意义。在移植后具有高相对丰度的总γδ T 细胞和 Vδ2+T 细胞的患者发生 II-IV 级 aGvHD 的累积发生率显著降低（p=0.03 和 p=0.04，分别）。Vδ2+T 细胞的高相对丰度也与 EBV 感染的发生率较低相关（p=0.02）。另一方面，患有 EBV 感染的患者在移植后第 100 天和第 180 天的绝对 Vδ1+T 细胞计数更高（p=0.046 和 0.038，分别），而没有 EBV 感染的患者则没有。在多变量时间平均分析（q<0.1）中，该结果仍然具有统计学意义。我们的结果表明，γδ T 细胞，特别是 Vδ2+T 细胞亚群在儿科 HSCT 后预防 aGvHD 和 EBV 感染的发展中起保护作用。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 HSCT 后 γδ T 细胞作为预后标志物和作为过继性 T 细胞转移策略的可能靶点。
