Format

Send to

Choose Destination
J Leukoc Biol. 2014 Dec;96(6):1165-75. doi: 10.1189/jlb.1TA0214-121RR. Epub 2014 Aug 25.

Technical advance: ascorbic acid induces development of double-positive T cells from human hematopoietic stem cells in the absence of stromal cells.

Author information

1
Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center, and mirelle.huijskens@maastrichtuniversity.nl.
2
Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center, and.
3
Department of Toxicogenomics, School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.

Abstract

The efficacy of donor HSCT is partly reduced as a result of slow post-transplantation immune recovery. In particular, T cell regeneration is generally delayed, resulting in high infection-related mortality in the first years post-transplantation. Adoptive transfer of in vitro-generated human T cell progenitors seems a promising approach to accelerate T cell recovery in immunocompromised patients. AA may enhance T cell proliferation and differentiation in a controlled, feeder-free environment containing Notch ligands and defined growth factors. Our experiments show a pivotal role for AA during human in vitro T cell development. The blocking of NOS diminished this effect, indicating a role for the citrulline/NO cycle. AA promotes the transition of proT1 to proT2 cells and of preT to DP T cells. Furthermore, the addition of AA to feeder cocultures resulted in development of DP and SP T cells, whereas without AA, a preT cell-stage arrest occurred. We conclude that neither DLL4-expressing feeder cells nor feeder cell conditioned media are required for generating DP T cells from CB and G-CSF-mobilized HSCs and that generation and proliferation of proT and DP T cells are greatly improved by AA. This technology could potentially be used to generate T cell progenitors for adoptive therapy.

KEYWORDS:

DLL4 protein; T cell precursor; adoptive cellular immunotherapy; transplantation

PMID:
25157026
DOI:
10.1189/jlb.1TA0214-121RR
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center