[PDF][PDF] Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro

TM Schmitt, JC Zúñiga-Pflücker - Immunity, 2002 - cell.com
Immunity, 2002cell.com
The molecular interactions provided by the thymic microenvironment that predicate T cell
development remain obscure. Here, we show that a bone marrow stromal cell line
ectopically expressing the Notch ligand Delta-like-1 loses its ability to support B cell
lymphopoiesis, but acquires the capacity to induce the differentiation of hematopoietic
progenitors into CD4 CD8 double-and single-positive T cells. Both γδ-TCR+ and αβ-TCR+ T
cells are generated, and CD8+ TCR hi cells produce γ-interferon following CD3/TCR …
Abstract
The molecular interactions provided by the thymic microenvironment that predicate T cell development remain obscure. Here, we show that a bone marrow stromal cell line ectopically expressing the Notch ligand Delta-like-1 loses its ability to support B cell lymphopoiesis, but acquires the capacity to induce the differentiation of hematopoietic progenitors into CD4 CD8 double- and single-positive T cells. Both γδ-TCR+ and αβ-TCR+ T cells are generated, and CD8+ TCRhi cells produce γ-interferon following CD3/TCR stimulation. These results establish that expression of Delta-like-1 on stromal cells provides key signals for the induction of T cell lineage commitment, stage-specific progenitor expansion, TCR gene rearrangement, and T cell differentiation in the absence of a thymus. Thus, it is likely that Delta-like-1/Notch interactions by the thymus underpin its unique ability to promote lineage commitment and differentiation of T cells.
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