| Autor: |
Smeets MF; Haematology and Leukaemia Unit, St Vincent's Institute of Medical Research, 9 Princes Street, Fitzroy, Victoria 3065, Australia., Mackenzie-Kludas C, Mohtashami M, Zhang HH, Zúñiga-Pflücker JC, Izon DJ |
| Jazyk: |
angličtina |
| Zdroj: |
International immunology [Int Immunol] 2013 Oct; Vol. 25 (10), pp. 589-99. Date of Electronic Publication: 2013 Aug 29. |
| DOI: |
10.1093/intimm/dxt025 |
| Abstrakt: |
The majority of T-cell development occurs in the thymus. Thymic epithelial cells are specialized cells that express NOTCH ligands and secrete specific cytokines required for normal T-cell lymphopoiesis. It has been demonstrated that OP9 cells derived from macrophage colony-stimulating factor (M-CSF)-deficient mice can support T-cell development when transduced with a NOTCH ligand, Delta-like 1 (Dll1). In this report, we have tested CSF-deficient mouse fibroblasts transduced with Dll1 for their ability to support T-cell differentiation. The data provided here demonstrate that CSF-deficient fibroblasts expressing DLL1 can support T-cell development. Indeed, co-cultures with these fibroblasts produced more T-cell progenitors compared with OP9-DL1 cultures. Addition of myeloid cytokines to OP9-DL1 co-cultures significantly inhibited T-cell development while CSF-deficient DLL1(+) fibroblasts retained partial T-cell differentiation. Taken together, these data imply that their lack of myeloid cytokines allows DLL1(+) fibroblasts to more efficiently generate T-cells. Development of this fibroblast system suggests that there is potential for generating human T-cell precursors via co-culture with human fibroblasts expressing DLL1 or DLL4. These T-cell precursors could be used for treating immunodeficient patients. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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