Institute of Immunology, Hannover Medical School, Hannover, Germany.
Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Nat Immunol. 2017 Apr;18(4):393-401. doi: 10.1038/ni.3686. Epub 2017 Feb 20.
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 (TRG and TRD) in the peripheral blood of healthy adults were stable over time. Although a large fraction of human TRG repertoires consisted of public sequences, the TRD repertoires 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.
为了研究人类 γδ T 细胞库在个体发生过程中是如何形成的，以及在造血干细胞 (HSCs) 移植后如何进行再生，我们应用基于 RNA 的下一代测序方法，在一项前瞻性队列研究中监测移植前后 γδ T 细胞抗原受体 (TCR) 库的动态。我们发现，健康成年人外周血中编码 γδ TCR（TRG 和 TRD）的重排基因的库随时间保持稳定。尽管人类 TRG 库的很大一部分由公共序列组成，但 TRD 库是私人的。在接受 HSC 移植的患者中，γδ T 细胞迅速重建；然而，它们的 TCR 库发生了深刻的改变。值得注意的是，巨细胞病毒激活患者中个别病毒反应性 γδ TCR 序列的克隆性增殖，为适应性抗病毒 γδ T 细胞免疫反应提供了强有力的证据。
