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

Leukemia. 2017 May;31(5):1145-1153. doi: 10.1038/leu.2016.321. Epub 2016 Nov 4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antigens, CD19*
  • Child
  • Child, Preschool
  • Graft Survival*
  • Hematologic Diseases / therapy*
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Infant
  • Lymphocyte Depletion / methods*
  • Receptors, Antigen, T-Cell, alpha-beta*
  • T-Lymphocytes / immunology*
  • Time Factors
  • Young Adult

Substances

  • Antigens, CD19
  • Receptors, Antigen, T-Cell, alpha-beta