| Literature DB >> 27811849 |
I V Zvyagin1,2, I Z Mamedov1,2, O V Tatarinova3, E A Komech1, E E Kurnikova3, E V Boyakova3, V Brilliantova3, L N Shelikhova3, D N Balashov3, M Shugay1,2,4, A L Sycheva1, S A Kasatskaya1, Y B Lebedev1, A A Maschan3,4, M A Maschan3,4, D M Chudakov1,2,4.
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.Entities:
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Year: 2016 PMID： 27811849 DOI： 10.1038/leu.2016.321
Source DB: PubMed Journal: Leukemia ISSN： 0887-6924 Impact factor: 11.528