T-cell frequencies of CD8+ γδ and CD27+ γδ cells in the stem cell graft predict the outcome after allogeneic hematopoietic cell transplantation

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Abstract

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 CD8+γδ 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 CD27+γδ 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 CD8+γδ 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.

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Acknowledgements

This study was supported by Stockholm county Council, Swedish research Council, Children Cancer Foundation, and Radiumhemmets Forskningsfonder.

Author contributions

MU supervised the study. AG and AS performed laboratory work and data analysis. EW, MS, and JM provided graft samples and clinical data. BÖ and MU interpreted the data. AG and MU wrote the manuscript. All coauthors critically revised the manuscript.

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Correspondence to Ahmed Gaballa or Michael Uhlin.

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Gaballa, A., Stikvoort, A., Önfelt, B. et al. T-cell frequencies of CD8+ γδ and CD27+ γδ cells in the stem cell graft predict the outcome after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant 54, 1562–1574 (2019) doi:10.1038/s41409-019-0462-z

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