| First Author | Smeets MF | Year | 2013 |
| Journal | Int Immunol | Volume | 25 |
| Issue | 10 | Pages | 589-99 |
| PubMed ID | 23988615 | Mgi Jnum | J:201880 |
| Mgi Id | MGI:5516124 | Doi | 10.1093/intimm/dxt025 |
| Citation | Smeets MF, et al. (2013) Removal of myeloid cytokines from the cellular environment enhances T-cell development in vitro. Int Immunol 25(10):589-99 |
| abstractText | 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. |
