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Genetic T-cell receptor diversity at 1 year following allogeneic hematopoietic stem cell transplantation.
Leukemia ( IF 11.4 ) Pub Date : 2019-11-26 , DOI: 10.1038/s41375-019-0654-y
Stéphane Buhler 1 , Florence Bettens 1 , Carole Dantin 2 , Sylvie Ferrari-Lacraz 1 , Marc Ansari 3 , Anne-Claire Mamez 2 , Stavroula Masouridi-Levrat 2 , Yves Chalandon 2 , Jean Villard 1
Affiliation  

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 CDR3β 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.

中文翻译:

同种异体造血干细胞移植后1年的遗传T细胞受体多样性。

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诸如条件,感染以及移植物抗宿主病(GVHD)等事件的影响。影响TCR多样性的因素对于微调捐赠者选择策略和优化护理标准非常重要。在这项工作中,TCRCDR3β区的免疫测序在HSCT发生1年后的116位完全嵌合受体及其移植前的各自供体的大型队列中进行。HSCT之前和之后的库重叠很小,支持从头重建是任何年龄的主要途径。在调查的参数中,患者和/或供体年龄的增加以及CMV感染/再激活增强的CMV阳性血清学状况与HSCT后1年多样性降低明显相关。研究表明,CMV特异的T细胞克隆会影响库的克隆性,同时会扩展有限数量的非CMV T细胞群体。有趣的是,除CMV感染/重新激活外,TCR多样性不能预测GCTHD,复发,死亡或HSCT后感染。
更新日期:2019-11-27
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