| Autor: |
Zvyagin, I V, Mamedov, I Z, Tatarinova, O V, Komech, E A, Kurnikova, E E, Boyakova, E V, Brilliantova, V, Shelikhova, L N, Balashov, D N, Shugay, M, Sycheva, A L, Kasatskaya, S A, Lebedev, Y B, Maschan, A A, Maschan, M A, Chudakov, D M |
| Zdroj: |
Leukemia; May 2017, Vol. 31 Issue: 5 p1145-1153, 9p |
| Abstrakt: |
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. |
| Databáze: |
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