Gaballa Ahmed, Stikvoort Arwen, Önfelt Björn, Mattsson Jonas, Sundin Mikael, Watz Emma, Uhlin Michael
Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden.
Bone Marrow Transplant. 2019 Oct;54(10):1562-1574. doi: 10.1038/s41409-019-0462-z. Epub 2019 Feb 5.
The impact of intra-graft T cells on the clinical outcome after allogeneic hematopoietic cell transplantation has been investigated. Most previous studies have focused on the role of αβ cells while γδ cells have received less attention. It has been an open question whether γδ cells are beneficial or not for patient outcome, especially with regards to graft versus host disease. In this study, graft composition of γδ cell subsets was analyzed and correlated to clinical outcome in 105 recipients who underwent allogeneic hematopoietic cell transplantation between 2013 and 2016. We demonstrate for the first time that grafts containing higher T-cell proportions of CD8γδ cells were associated with increased cumulative incidence of acute graft versus host disease grade II-III (50% vs 22.6%; P = 0.008). Additionally, graft T-cell frequency of CD27γδ cells was inversely correlated with relapse (P = 0.006) and CMV reactivation (P = 0.05). We conclude that clinical outcome after allogeneic hematopoietic cell transplantation is influenced by the proportions of distinct γδ cell subsets in the stem cell graft. We also provide evidence that CD8γδ cells are potentially alloreactive and may play a role in acute graft versus host disease. This study illustrates the importance of better understanding of the role of distinct subsets of γδ cells in allogeneic hematopoietic cell transplantation.
同种异体造血细胞移植后移植物内T细胞对临床结局的影响已得到研究。以往大多数研究聚焦于αβ细胞的作用,而γδ细胞受到的关注较少。γδ细胞对患者结局是否有益,尤其是在移植物抗宿主病方面,一直是个悬而未决的问题。在本研究中,分析了105例在2013年至2016年间接受同种异体造血细胞移植的受者的γδ细胞亚群移植物组成,并将其与临床结局相关联。我们首次证明,含有较高比例CD8γδ细胞的移植物与急性移植物抗宿主病II - III级累积发生率增加相关(50%对22.6%;P = 0.008)。此外,CD27γδ细胞的移植物T细胞频率与复发(P = 0.006)和巨细胞病毒再激活(P = 0.05)呈负相关。我们得出结论,同种异体造血细胞移植后的临床结局受干细胞移植物中不同γδ细胞亚群比例的影响。我们还提供证据表明,CD8γδ细胞可能具有同种异体反应性,并可能在急性移植物抗宿主病中发挥作用。这项研究说明了更好地理解γδ细胞不同亚群在同种异体造血细胞移植中的作用的重要性。