In vitro-differentiated T/natural killer-cell progenitors derived from human CD34+ cells mature in the thymus

Blood. 2010 Jan 14;115(2):261-4. doi: 10.1182/blood-2009-05-223990. Epub 2009 Oct 14.


Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is a treatment option for patients with hematopoietic malignancies that is hampered by treatment-related morbidity and mortality, in part the result of opportunistic infections, a direct consequence of delayed T-cell recovery. Thymic output can be improved by facilitation of thymic immigration, known to require precommitment of CD34(+) cells. We demonstrate that Delta-like ligand-mediated predifferentiation of mobilized CD34(+) cells in vitro results in a population of thymocyte-like cells arrested at a T/natural killer (NK)-cell progenitor stage. On intrahepatic transfer to Rag2(-/-)gamma(c)(-/-) mice, these cells selectively home to the thymus and differentiate toward surface T-cell receptor-alphabeta(+) mature T cells considerably faster than animals transplanted with noncultured CD34(+) cells. This finding creates the opportunity to develop an early T-cell reconstitution therapy to combine with HSCT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34*
  • Cell Differentiation
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Lymphoid Progenitor Cells / cytology
  • Lymphoid Progenitor Cells / immunology
  • Lymphoid Progenitor Cells / metabolism*
  • Mice
  • Mice, Knockout
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Thymus Gland / cytology
  • Thymus Gland / immunology
  • Thymus Gland / metabolism*
  • Transplantation, Heterologous
  • Transplantation, Homologous


  • Antigens, CD34
  • DNA-Binding Proteins
  • Rag2 protein, mouse