Publication details

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

Authors	ZVYAGIN I.V. MAMEDOV Ilgar TATARINOVA O.V. KOMECH E.A. KURNIKOVA E.E. BOYAKOVA E.V. BRILLIANTOVA V. SHELIKHOVA L.N. BALASHOV D.N. SHUGAY Mikhail SYCHEVA A.L KASATSKAYA S.A. LEBEDEV Y.B. MASCHAN A.A MASCHAN M.A. CHUDAKOV Dmitriy
Year of publication	2017
Type	Article in Periodical
Magazine / Source	Leukemia
MU Faculty or unit	Central European Institute of Technology
Citation
web	https://www.nature.com/articles/leu2016321.pdf
Doi	http://dx.doi.org/10.1038/leu.2016.321
Keywords	BONE-MARROW-TRANSPLANTATION; HLA-IDENTICAL SIBLINGS; VERSUS-HOST-DISEASE; ACUTE-LEUKEMIA; CYTOMEGALOVIRUS REACTIVATION; COMBINED IMMUNODEFICIENCY; VIRUS INFECTION; REPERTOIRE; DEPLETION; TCR
Description	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.