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Leukemia. 2017 May;31(5):1145-1153. doi: 10.1038/leu.2016.321. Epub 2016 Nov 4.

Tracking T-cell immune reconstitution after TCRαβ/CD19-depleted hematopoietic cells transplantation in children.

Author information

1
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow, Russia.
2
CEITEC MU, Masaryk University, Brno, Czech republic.
3
Dmitrii Rogachev Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
4
Pirogov Russian National Research Medical University, Moscow, Russia.

Abstract

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.

PMID:
27811849
DOI:
10.1038/leu.2016.321
[Indexed for MEDLINE]

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