Leukemia, 2017, 31(5):1145-1153

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

All rights reserved. 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.

Zvyagin IV, Mamedov IZ, Tatarinova OV, Komech EA, Kurnikova EE, Boyakova EV, Brilliantova V, Shelikhova LN, Balashov DN, Shugay M, Sycheva AL, Kasatskaya SA, Lebedev YB, Maschan AA, Maschan MA, Chudakov DM

IBCH: 3232
Ссылка на статью в журнале: http://www.nature.com/doifinder/10.1038/leu.2016.321
Кол-во цитирований на 10.2023: 39
Данные статьи проверены модераторами 2017-05-01

Список научных проектов, где отмечена публикация

  1. Изучение динамики системы клеточного адаптивного иммунитета при флавивирусной инфекции (6 Января 2015 года — 31 Декабря 2019 года). Лебедев Ю.Б.. Грант, РНФ.