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Induction of T-cell development from human cord blood hematopoietic stem cells by Delta-like 1 in vitro.

La Motte-Mohs RN, Herer E, Zúñiga-Pflücker JC

Department of Immunology, University of Toronto, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada.

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.

Published 3 February 2005 in Blood, 105(4): 1431-9.
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