Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro.
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 gammadelta-TCR(+) and alphabeta-TCR(+) T cells are generated, and CD8(+) TCR(hi) cells produce gamma-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.
Schmitt
Thomas M
TM
Department of Immunology, University of Toronto, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada.
Zúñiga-Pflücker
Juan Carlos
JC
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D019070:Cell Lineage / Q000235:genetics* / Q000276:immunology*; D018507:Gene Expression Regulation, Developmental / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000276:immunology; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D017154:Stromal Cells / Q000166:cytology / Q000276:immunology
D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C064045:delta protein