Tracking T-cell immune reconstitution after TCRαβ/CD19-depleted hematopoietic cells transplantation in children.
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.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow, Russia.|CEITEC MU, Masaryk University, Brno, Czech republic.
I V
IV
Zvyagin
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow, Russia.|CEITEC MU, Masaryk University, Brno, Czech republic.
I Z
IZ
Mamedov
Dmitrii Rogachev Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
O V
OV
Tatarinova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow, Russia.
E A
EA
Komech
Dmitrii Rogachev Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
E E
EE
Kurnikova
Dmitrii Rogachev Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
E V
EV
Boyakova
Dmitrii Rogachev Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
V
V
Brilliantova
Dmitrii Rogachev Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
L N
LN
Shelikhova
Dmitrii Rogachev Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
D N
DN
Balashov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow, Russia.|CEITEC MU, Masaryk University, Brno, Czech republic.|Pirogov Russian National Research Medical University, Moscow, Russia.
M
M
Shugay
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow, Russia.
A L
AL
Sycheva
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow, Russia.
S A
SA
Kasatskaya
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow, Russia.
Y B
YB
Lebedev
Dmitrii Rogachev Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.|Pirogov Russian National Research Medical University, Moscow, Russia.
A A
AA
Maschan
Dmitrii Rogachev Federal Research Center for Pediatric Hematology, Oncology and Immunology, Moscow, Russia.|Pirogov Russian National Research Medical University, Moscow, Russia.
M A
MA
Maschan
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Science, Moscow, Russia.|CEITEC MU, Masaryk University, Brno, Czech republic.|Pirogov Russian National Research Medical University, Moscow, Russia.
D M
DM
Chudakov
D000293:Adolescent; D018941:Antigens, CD19; D002648:Child; D002675:Child, Preschool; D006085:Graft Survival; D006402:Hematologic Diseases / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007223:Infant; D008212:Lymphocyte Depletion / Q000379:methods*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013601:T-Lymphocytes / Q000276:immunology*; D013997:Time Factors; D055815:Young Adult
D018941:Antigens, CD19; D016693:Receptors, Antigen, T-Cell, alpha-beta