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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F17%3A00100338" target="_blank" >RIV/00216224:14740/17:00100338 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.nature.com/articles/leu2016321.pdf" target="_blank" >https://www.nature.com/articles/leu2016321.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/leu.2016.321" target="_blank" >10.1038/leu.2016.321</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30204 - Oncology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Leukemia

ISSN

0887-6924

e-ISSN

—

Svazek periodika

31

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

1145-1153

Kód UT WoS článku

000400464800013

EID výsledku v databázi Scopus

2-s2.0-85001832885