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Abstract：
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.
摘要：
γδ（γδ）T细胞占人类T细胞库的一小部分，但在异基因造血干细胞移植（allo-HSCT）的背景下，在介导抗感染和抗肿瘤作用中起重要作用。我们进行了一项前瞻性研究，以分析不同移植方式对γδT细胞和亚群免疫重建的影响。平行分析CD3、CD4和CD8T细胞。其次,我们研究了γδT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局的影响.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）供体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。在单变量分析中,MRD患者在时间点+30、+60、+100(分别为p<0.001)和+180(p<0.01)表现出明显高于MUD患者的Vδ2+T细胞。这些结果在多变量分析中仍然显著。具有高相对丰度的总γδT细胞和Vδ2T细胞恢复的患者移植后II-IV级aGvHD的累积发生率显着降低（分别为p=0.03和p=0.04）。高相对丰度的Vδ2+T细胞也与较低的EBV感染发生率相关(p=0.02)。另一方面，与没有EBV感染的患者相比，EBV感染的患者在移植后第100天和第180天显示出更高的绝对Vδ1T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(q<0.1)中保持显著。我们的结果表明，γδT细胞，尤其是Vδ2T细胞亚群对小儿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γδT细胞作为HSCT后的预后标志物和过继性T细胞转移策略的可能靶标。
