Removal of myeloid cytokines from the cellular environment enhances T-cell development in vitro

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Abstract

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 CSFdeficient 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. © The Japanese Society for Immunology. 2013. All rights reserved.

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Smeets, M. F. M. A., Mackenzie-Kludas, C., Mohtashami, M., Zhang, H. H., Zúñiga-Pflücker, J. C., & Izon, D. J. (2013). Removal of myeloid cytokines from the cellular environment enhances T-cell development in vitro. International Immunology, 25(10), 589–599. https://doi.org/10.1093/intimm/dxt025

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