A stromal cell free culture system generates mouse pro-t cells that can reconstitute t-cell compartments in vivo
Gehre, Nadine Nusser, Anja von Muenchow, Lilly Tussiwand, Roxane Engdahl, Corinne Capoferri, Giuseppina Bosco, Nabil Ceredig, Rhodri Rolink, Antonius G.
Gehre, Nadine
Nusser, Anja
von Muenchow, Lilly
Tussiwand, Roxane
Engdahl, Corinne
Capoferri, Giuseppina
Bosco, Nabil
Ceredig, Rhodri
Rolink, Antonius G.
Repository DOI
Publication Date
2014-12-16
Keywords
bm transplantation, lymphopenia, notch ligand delta-like 4 (dl4), t-cell development, treg cell, hematopoietic stem-cells, bone-marrow-transplantation, deficiency syndrome aids, natural-killer-cell, cord blood-cells, delta-like 4, c-kit, lineage commitment, immune reconstitution, repopulating ability
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Article
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Citation
Gehre, Nadine; Nusser, Anja; von Muenchow, Lilly; Tussiwand, Roxane; Engdahl, Corinne; Capoferri, Giuseppina; Bosco, Nabil; Ceredig, Rhodri; Rolink, Antonius G. (2014). A stromal cell free culture system generates mouse pro-t cells that can reconstitute t-cell compartments in vivo. European Journal of Immunology 45 (3), 932-942
Abstract
T-cell lymphopenia following BM transplantation or diseases such as AIDS result in immunodeficiency. Novel approaches to ameliorate this situation are urgently required. Herein, we describe a novel stromal cell free culture system in which Lineage(-)Sca1(+)c-kit(+) BM hematopoietic progenitors very efficiently differentiate into pro-T cells. This culture system consists of plate-bound Delta-like 4 Notch ligand and the cytokines SCF and IL-7. The pro-T cells developing in these cultures express CD25, CD117, and partially CD44; express cytoplasmic CD3 epsilon; and have their TCR locus partially D-J rearranged. They could be expanded for over 3 months and used to reconstitute the T-cell compartments of sublethally irradiated T-cell-deficient CD3 epsilon(-/-) mice or lethally irradiated WT mice. Pro-T cells generated in this system could partially correct the T-cell lymphopenia of pre-T-/- mice. However, reconstituted CD3 epsilon(-/-) mice suffered from a wasting disease that was prevented by co-injection of purified CD4(+) CD25(high) WT Treg cells. In a T-cell-sufficient or T-lymphopenic setting, the development of disease was not observed. Thus, this in vitro culture system represents a powerful tool to generate large numbers of pro-T cells for transplantation and possibly with clinical applications.
Funder
Publisher
Wiley-Blackwell
Publisher DOI
10.1002/eji.201444681
Rights
Attribution-NonCommercial-NoDerivs 3.0 Ireland