Genetic T-cell receptor diversity at 1 year following allogeneic hematopoietic stem cell transplantation
Genetic T-cell receptor diversity at 1 year following allogeneic hematopoietic stem cell transplantation
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DOI：
10.1038/s41375-019-0654-y
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发表时间：
2020-05-01
期刊：
影响因子：
11.4
通讯作者：
Villard, Jean
中科院分区：
文献类型：
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作者：
Buhler, Stephane;Bettens, Florence;Villard, Jean
异基因造血干细胞移植（HSCT）后，免疫重建导致新的T细胞库的发展。免疫重建可能会受到条件反射、感染和移植物抗宿主病（GVHD）等事件的影响。影响TCR多样性的因素对于微调供体选择策略和优化护理标准具有重要意义。在这项工作中，在HSCT后1年的116名完全嵌合受体及其各自的供体在移植前的大队列中进行TCR CDR 3 β区的免疫测序。HSCT前后的库重叠是最小的，支持从头重建作为任何年龄的主要途径。在研究的参数中，患者和/或供体年龄的增加以及CMV感染/再激活加强的阳性CMV血清学状态与HSCT后1年的多样性降低显著相关。CMV特异性T细胞克隆显示影响库的克隆性，同时扩增有限数量的非CMV T细胞群体。有趣的是，除了CMV感染/再活化，TCR多样性不能预测GVHD、复发、死亡或HSCT后感染。
After allogeneic hematopoietic stem cell transplantation (HSCT), immune reconstitution leads to the development of a new T-cell repertoire. Immune reconstitution could be influenced by events such as conditioning, infections, and graft versus host disease (GVHD). Factors influencing the TCR diversity are of great interest to fine-tune the strategy for donor selection and to optimize standard of care. In this work, immunosequencing of the TCR CDR3 beta region was carried out in a large cohort of 116 full chimeric recipients at 1 year post-HSCT and their respective donors prior to transplantation. The repertoire overlap before and after HSCT was minimal, supporting de novo reconstitution as a primary pathway at any age. Among the parameters investigated, increased patient and/or donor age as well as positive CMV serologic status reinforced by CMV infection/reactivation were the ones significantly associated with a reduced diversity at 1 year post-HSCT. CMV-specific T-cell clones were shown to influence the clonality of the repertoire alongside the expansion of limited numbers of non-CMV T-cell populations. Interestingly, at the exception of CMV infection/reactivation, TCR diversity was not predictive of GVHD, relapse, death, or infections post-HSCT.