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In vitro-differentiated T/natural killer-cell progenitors derived from human CD34+ cells mature in the thymus.
- Source :
-
Blood [Blood] 2010 Jan 14; Vol. 115 (2), pp. 261-4. Date of Electronic Publication: 2009 Oct 14. - Publication Year :
- 2010
-
Abstract
- 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.
- Subjects :
- Animals
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
Lymphoid Progenitor Cells cytology
Lymphoid Progenitor Cells immunology
Mice
Mice, Knockout
T-Lymphocytes cytology
T-Lymphocytes immunology
Thymus Gland cytology
Thymus Gland immunology
Transplantation, Heterologous
Transplantation, Homologous
Antigens, CD34
Killer Cells, Natural metabolism
Lymphoid Progenitor Cells metabolism
T-Lymphocytes metabolism
Thymus Gland metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 115
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 19828700
- Full Text :
- https://doi.org/10.1182/blood-2009-05-223990