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

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  • Additional Information
    • Source:
      Publisher: Nature Publishing Group, Specialist Journals Country of Publication: England NLM ID: 8704895 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5551 (Electronic) Linking ISSN: 08876924 NLM ISO Abbreviation: Leukemia Subsets: MEDLINE
    • Publication Information:
      Publication: 2000- : London : Nature Publishing Group, Specialist Journals
      Original Publication: [Baltimore, Md.] : Williams & Wilkins, [c1987-
    • Subject Terms:
      Antigens, CD19* ; Graft Survival* ; Receptors, Antigen, T-Cell, alpha-beta*; Hematologic Diseases/*therapy ; Hematopoietic Stem Cell Transplantation/*methods ; Lymphocyte Depletion/*methods ; T-Lymphocytes/*immunology; Adolescent ; Child ; Child, Preschool ; Humans ; Infant ; Time Factors ; Young Adult
    • 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.
    • Accession Number:
      0 (Antigens, CD19)
      0 (Receptors, Antigen, T-Cell, alpha-beta)
    • Publication Date:
      Date Created: 20161105 Date Completed: 20170912 Latest Revision: 20180527
    • Publication Date:
      20221213
    • Accession Number:
      10.1038/leu.2016.321
    • Accession Number:
      27811849