Induction of T-cell development from human cord blood hematopoietic stem cells by Delta-like 1 in vitro.
The Notch signaling pathway plays a key role at several stages of T-lymphocyte differentiation. However, it remained unclear whether signals induced by the Notch ligand Delta-like 1 could support full T-cell differentiation from a defined source of human hematopoietic stem cells (HSCs) in vitro. Here, we show that human cord blood-derived HSCs cultured on Delta-like 1-expressing OP9 stromal cells undergo efficient T-cell lineage commitment and sustained T-cell differentiation. A normal stage-specific program of T-cell development was observed, including the generation of CD4 and CD8 alpha beta-T-cell receptor (TCR)-bearing cells. Induction of T-cell differentiation was dependent on the expression of Delta-like 1 by the OP9 cells. Stimulation of the in vitro-differentiated T cells by TCR engagement induced the expression of T-cell activation markers and costimulatory receptors. These results establish an efficient in vitro coculture system for the generation of T cells from human HSCs, providing a new avenue for the study of early T-cell differentiation and function.
La Motte-Mohs
Ross N
RN
Department of Immunology, University of Toronto, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada.
Herer
Elaine
E
Zúñiga-Pflücker
Juan Carlos
JC
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D019070:Cell Lineage / Q000276:immunology; D018920:Coculture Techniques; D005312:Fetal Blood / Q000166:cytology* / Q000502:physiology*; D006023:Glycoproteins / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*
D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064045:delta protein