Although thymus-independent donor-derived T cell expansion may determine the occurrence of graft-versus-host disease (GVHD) and relapse after transplantation, the characteristics and dynamics of the expansion process remain unclear. To address this issue, we monitored T cell receptor β repertoire at day 0, day 28, and day 61 after transplantation in 30 patients with hematologic malignancies by next-generation sequencing. The clonality index showed an increasing clonality over time (P = .001). The top 200 clonotypes accounted for more than half of the total clonotypes (median frequency, 63.55%) at day 61, and there was a remarkable overlapping between the top 200 clonotypes of each repertoire and its former repertoire (>50%). A normalized index, called the T Cell Response Index (TCRI), was designed on the basis of rank-shift analysis to quantify antigen-driven expansion. The TCRI during the first month was not related to relapse or GVHD (P> .05), whereas the TCRI during the second month was related to relapse (P = .006). Recipients with a TCRI below 1.0 during the second month had a higher cumulative relapse rate (31.25% versus 0%, P = .0323) and had a lower 1-year survival rate (56.25% versus 78.57%, P = .281). The clonotypes with strong competitiveness in the second month in the nonrelapse group preferentially used TRBV2, TRBV12-3, TRBJ1-1 and TRBJ1-5 segments (P< .01). In conclusion, homeostatic expansion predominates in the first month due to nonspecific T cell proliferation, whereas antigen-driven expansion predominates in the second month and results in a graft-versus-tumor (GvT) effect. Moreover, TCRI could serve as a quantitative indicator of GvT against relapse within the first year. The difference in V and J segment usage reveals that T cells responsible for potent GvT effect are similar among patients.

中文翻译：

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移植患者胸腺非依赖供体来源的T细胞扩增的定量分析。

尽管不依赖胸腺的供体来源的T细胞扩增可能决定移植物抗宿主病（GVHD）的发生以及移植后的复发，但扩增过程的特征和动力学仍不清楚。为了解决这个问题，我们通过下一代测序方法监测了30例血液系统恶性肿瘤患者在移植后第0天，第28天和第61天的T细胞受体β库。克隆性指数显示出克隆性随着时间的推移而增加（P = .001）。在第61天，排名前200位的克隆型占全部克隆型的一半以上（中位数频率为63.55％），并且每个曲目库的前200个克隆型与之前的曲目（> 50％）之间存在明显的重叠。标准化索引，称为T细胞反应指数（TCRI），在等级变动分析的基础上设计了用于定量抗原驱动的扩增的蛋白。第一个月的TCRI与复发或GVHD无关（P> .05），而第二个月的TCRI与复发有关（P = .006）。第二个月TCRI低于1.0的接收者具有较高的累积复发率（31.25％对0％，P = .0323），较低的1年生存率（56.25％对78.57％，P = .281）。非复发组第二个月具有较强竞争能力的克隆型优先使用TRBV2，TRBV12-3，TRBJ1-1和TRBJ1-5区段（P <.01）。总之，由于非特异性T细胞增殖，稳态扩张在第一个月占主导地位，而抗原驱动的扩张在第二个月占主导地位，并导致移植物抗肿瘤（GvT）效应。而且，TCRI可以作为GvT预防第一年复发的定量指标。V和J节用法的差异表明，负责有效GvT效应的T细胞在患者之间相似。