Tracking T-cell immune reconstitution after TCR alpha beta /CD19-depleted hematopoietic cells transplantation in children

• Published in: Leukemia Vol. 31; no. 5; pp. 1145 - 1153
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: 01-05-2017
• ISSN: 0887-6924
• DOI: 10.1038/leu.2016.321

alpha beta T-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 TCR alpha beta -/CD19-depleted transplantation in children. We demonstrate that seemingly early reconstitution of alpha beta T-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 TCR beta diversity are mostly provided by the newly produced T cells. We also demonstrate that high TCR beta 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 TCR alpha beta -/CD19-depleted transplantation protocols should be directed toward providing more efficient T-cell defense in the first months after transplantation.