First Author | Mohtashami M | Year | 2006 |
Journal | J Immunol | Volume | 176 |
Issue | 2 | Pages | 730-4 |
PubMed ID | 16393955 | Mgi Jnum | J:126600 |
Mgi Id | MGI:3761731 | Doi | 10.4049/jimmunol.176.2.730 |
Citation | Mohtashami M, et al. (2006) Three-dimensional architecture of the thymus is required to maintain delta-like expression necessary for inducing T cell development. J Immunol 176(2):730-4 |
abstractText | The three-dimensional microarchitecture of the thymus plays a unique role in directing T cell lineage commitment and development. This is supported by the fact that, in contrast to fetal thymic organ cultures, thymic stromal cell monolayer cultures (TSMC) fail to support T lymphopoiesis. Nevertheless, OP9-DL1 cell monolayer cultures induce T lineage commitment and differentiation. Thus, the inability of TSMC to support T lymphopoiesis may be due to a loss of Notch ligand expression and/or function during culture. In this study, we report that, in contrast to fetal thymic organ cultures, TSMC fail to maintain expression of the Notch ligands, Delta-like (Dll) 1 and Dll4, and concomitantly lose the ability to support T lymphopoiesis. Importantly, ectopic re-expression of Dll1 or Dll4 is sufficient to restore the ability of TSMC to support T lymphopoiesis. These findings demonstrate that maintenance of endogenous Dll1 or Dll4 expression by thymic stromal cells is required for the commitment and differentiation of T cells in the absence of a three-dimensional microenvironment. |