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

I. V. Zvyagin, I. Z. Mamedov, O. V. Tatarinova, E. A. Komech, E. E. Kurnikova, E. V. Boyakova, V. Brilliantova, L. N. Shelikhova, D. N. Balashov, M. Shugay, A. L. Sycheva, S. A. Kasatskaya, Y. B. Lebedev, A. A. Maschan, M. A. Maschan, D. M. Chudakov

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1145-1153
Number of pages9
JournalLeukemia
Volume31
Issue number5
DOIs
Publication statusPublished - 1 May 2017
Externally publishedYes

Fingerprint

Dive into the research topics of 'Tracking T-cell immune reconstitution after TCRαβ/CD19-depleted hematopoietic cells transplantation in children'. Together they form a unique fingerprint.

Cite this