αβT-cell-depleted allogeneic hematopoietic cell transplantation holds promise for the safe and accessible therapy of both malignant and non-malignant blood disorders. Here we employed molecular barcoding normalized T-cell receptor (TCR) profiling to quantitatively track T-cell immune reconstitution after TCRαβ-/CD19-depleted transplantation in children. We demonstrate that seemingly early reconstitution of αβT-cell counts 2 months after transplantation is based on only several hundred rapidly expanded clones originating from non-depleted graft cells. In further months, frequency of these hyperexpanded clones declines, and after 1 year the observed T-cell counts and TCRβ diversity are mostly provided by the newly produced T cells. We also demonstrate that high TCRβ diversity at day 60 observed for some of the patients is determined by recipient T cells and intrathymic progenitors that survived conditioning regimen. Our results indicate that further efforts on optimization of TCRαβ-/CD19-depleted transplantation protocols should be directed toward providing more efficient T-cell defense in the first months after transplantation.
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The collection and clinical analysis of samples was supported by Russian Science Foundation grant no 14-35-00105. TCR library preparation and sequencing was supported by Russian Science Foundation grant no 15-15-00178. Zvyagin I is supported by grant MK-4583.2015.4. The work was carried out in part using equipment provided by the Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry Core Facility (CKP IBCH). Hematopoietic stem cell transplant program at Dmitriy Rogachev Federal center of pediatric hematology, oncology and immunology is kindly supported by charitable fund ‘Podari Zhizn’. We thank our donors, physicians and nursing staff of the hematopoietic stem cell transplantation department.
The authors declare no conflict of interest.
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Zvyagin, I., Mamedov, I., Tatarinova, O. et al. Tracking T-cell immune reconstitution after TCRαβ/CD19-depleted hematopoietic cells transplantation in children. Leukemia 31, 1145–1153 (2017). https://doi.org/10.1038/leu.2016.321
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