| First Author | Gehre N | Year | 2015 |
| Journal | Eur J Immunol | Volume | 45 |
| Issue | 3 | Pages | 932-42 |
| PubMed ID | 25408420 | Mgi Jnum | J:222612 |
| Mgi Id | MGI:5644927 | Doi | 10.1002/eji.201444681 |
| Citation | Gehre N, et al. (2015) A stromal cell free culture system generates mouse pro-T cells that can reconstitute T-cell compartments in vivo. Eur J Immunol 45(3):932-42 |
| abstractText | 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. |
