A stromal cell free culture system generates mouse pro-T cells that can reconstitute T-cell compartments in vivo

Gehre, Nadine and Nusser, Anja and von Muenchow, Lilly and Tussiwand, Roxane and Engdahl, Corinne and Capoferri, Giuseppina and Bosco, Nabil and Ceredig, Rhodri and Rolink, Antonius G.. (2015) 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). pp. 932-942.

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Official URL: https://edoc.unibas.ch/62503/

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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 CD3epsilon; and have their TCRbeta 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 CD3epsilon(-/-) mice or lethally irradiated WT mice. Pro-T cells generated in this system could partially correct the T-cell lymphopenia of pre-Talpha(-/-) mice. However, reconstituted CD3epsilon(-/-) 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Immune Regulation (Tussiwand)
UniBasel Contributors:Tussiwand, Roxane
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Dec 2018 10:42
Deposited On:01 Dec 2018 10:42

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