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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1431-1439.
Prepublished online as a Blood First Edition Paper on October 19, 2004; DOI 10.1182/blood-2004-04-1293.
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Submitted April 13, 2004
Accepted September 17, 2004
Induction of T cell development from human cord blood hematopoietic stem cells by Delta-like 1 in vitro
Ross N La Motte-Mohs, Elaine Herer, and Juan Carlos Zuniga-Pflucker*
Department of Immunology, University of Toronto, Sunnybrook & Women's College Health Sciences Centre, Toronto, Ontario, Canada
Women's College Ambulatory Care Centre, The Women's College Campus of Sunnybrook and Women's Health Sciences Centre, Toronto, Ontario, Canada
* Corresponding author; email: jc.zuniga.pflucker{at}utoronto.ca.
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 ab-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.
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