Human γδ T cells are quickly reconstituted after stem-cell transplantation and show adaptive clonal expansion in response to viral infection
Human γδ T cells are quickly reconstituted after stem-cell transplantation and show adaptive clonal expansion in response to viral infection
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DOI：
10.1038/ni.3686
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发表时间：
2017-04-01
影响因子：
30.5
通讯作者：
Prinz，Immo
中科院分区：
文献类型：
--
作者：
Ravens，Sarina;Schultze-Florey，Christian;Prinz，Immo
为了研究人γδ T细胞库在个体发育过程中如何形成以及在造血干细胞（HSC）移植后如何再生，我们在一项前瞻性队列研究中应用基于RNA的下一代测序方法来监测移植前后γδ T细胞抗原受体（TCR）库的动态。我们发现，健康成人外周血中编码γδ TCR的重排基因（TRGandTRD）库随时间推移而稳定。虽然人类的TRGrepertoires的很大一部分由公共序列组成，但TRDrepertoires是私人的。在接受HSC移植的患者中，γδ T细胞迅速重建;然而，它们深刻地改变了TCR库。值得注意的是，巨细胞病毒再活化患者中单个病毒反应性γδ TCR序列的克隆增殖揭示了适应性抗病毒γδ T细胞免疫应答的强有力证据。
To investigate how the human γδ T cell pool is shaped during ontogeny and how it is regenerated after transplantation of hematopoietic stem cells (HSCs), we applied an RNA-based next-generation sequencing approach to monitor the dynamics of the repertoires of γδ T cell antigen receptors (TCRs) before and after transplantation in a prospective cohort study. We found that repertoires of rearranged genes encoding γδ TCRs (TRGandTRD) in the peripheral blood of healthy adults were stable over time. Although a large fraction of humanTRGrepertoires consisted of public sequences, theTRDrepertoires were private. In patients undergoing HSC transplantation, γδ T cells were quickly reconstituted; however, they had profoundly altered TCR repertoires. Notably, the clonal proliferation of individual virus-reactive γδ TCR sequences in patients with reactivation of cytomegalovirus revealed strong evidence for adaptive anti-viral γδ T cell immune responses.