A stromal cell free culture system generates mouse pro-T cells that can reconstitute T-cell compartments in vivo
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim..
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 CD3ε; and have their TCRβ 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 CD3ε(-/-) mice or lethally irradiated WT mice. Pro-T cells generated in this system could partially correct the T-cell lymphopenia of pre-Tα(-/-) mice. However, reconstituted CD3ε(-/-) 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:45 |
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| Enthalten in: |
European journal of immunology - 45(2015), 3 vom: 04. März, Seite 932-42 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gehre, Nadine [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.05.2015 Date Revised 09.12.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/eji.201444681 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM243646585 |
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| 245 | 1 | 2 | |a A stromal cell free culture system generates mouse pro-T cells that can reconstitute T-cell compartments in vivo |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. | ||
| 520 | |a 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 CD3ε; and have their TCRβ 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 CD3ε(-/-) mice or lethally irradiated WT mice. Pro-T cells generated in this system could partially correct the T-cell lymphopenia of pre-Tα(-/-) mice. However, reconstituted CD3ε(-/-) 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a BM transplantation | |
| 650 | 4 | |a Lymphopenia | |
| 650 | 4 | |a Notch ligand Delta-like 4 (DL4) | |
| 650 | 4 | |a T-cell development | |
| 650 | 4 | |a Treg cell | |
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| 650 | 7 | |a Antigens, CD |2 NLM | |
| 650 | 7 | |a CD3 Complex |2 NLM | |
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| 650 | 7 | |a Receptors, Antigen, T-Cell, alpha-beta |2 NLM | |
| 700 | 1 | |a Nusser, Anja |e verfasserin |4 aut | |
| 700 | 1 | |a von Muenchow, Lilly |e verfasserin |4 aut | |
| 700 | 1 | |a Tussiwand, Roxane |e verfasserin |4 aut | |
| 700 | 1 | |a Engdahl, Corinne |e verfasserin |4 aut | |
| 700 | 1 | |a Capoferri, Giuseppina |e verfasserin |4 aut | |
| 700 | 1 | |a Bosco, Nabil |e verfasserin |4 aut | |
| 700 | 1 | |a Ceredig, Rhodri |e verfasserin |4 aut | |
| 700 | 1 | |a Rolink, Antonius G |e verfasserin |4 aut | |
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