Title: Removal of myeloid cytokines from the cellular environment enhances T-cell development in vitro
Authors: Smeets, MFMA
Mackenzie-Kludas, C
Mohtashami, M
Zhang, HH
Zuniga-Pflucker, JC
Izon, DJ
Issue Year: 2013
Publisher OXFORD UNIV PRESS
Series INTERNATIONAL IMMUNOLOGY: 25(10): 589-599
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 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.
URI: https://publications.svi.edu.au/publications/1733
ISSN 0953-8178
Other Identifiers 10.1093/intimm/dxt025
Publication type Article