Induction of T Cell Development from Hematopoietic Progenitor Cells by Delta-like-1 In Vitro
2002; Cell Press; Volume: 17; Issue: 6 Linguagem: Inglês
10.1016/s1074-7613(02)00474-0
ISSN1097-4180
AutoresThomas M. Schmitt, Juan Carlos Zúñiga‐Pflücker,
Tópico(s)Epigenetics and DNA Methylation
ResumoThe 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.
Referência(s)