Entry into the thymic microenvironment triggers Notch activation in the earliest migrant T cell progenitors
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Entry into the thymic microenvironment triggers Notch activation in the earliest migrant T cell progenitors. / Harman, Ben; Jenkinson, Eric; Anderson, Graham.
In: Journal of Immunology, Vol. 170, No. 3, 01.02.2003, p. 1299-303.Research output: Contribution to journal › Article
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T1 - Entry into the thymic microenvironment triggers Notch activation in the earliest migrant T cell progenitors
AU - Harman, Ben
AU - Jenkinson, Eric
AU - Anderson, Graham
PY - 2003/2/1
Y1 - 2003/2/1
N2 - Interactions between T cell precursors and thymic stromal cells are essential during thymocyte development. However, the role of the thymus in initial commitment of lymphoid progenitors to the T lineage remains controversial, with data providing evidence for both extra- and intrathymic commitment mechanisms. In this context, it is clear that Notch1 is an important mediator during initiation of T cell development. Here we have analyzed the mechanisms regulating Notch activation in lymphoid precursors at extrathymic sites and in the thymus, including stages representing the first wave of embryonic thymus colonization on embryonic day 12 of gestation. We show that Notch activation in migrant lymphoid precursors requires entry into the thymic microenvironment where they are exposed to Notch ligands expressed by immature thymic epithelial cells. Moreover, continued Notch signaling in such precursors requires sustained interactions with Notch ligands. Collectively, these findings suggest a role for Notch in an intrathymic mechanism of T cell lineage commitment involving sustained interactions with Notch ligand bearing thymic epithelium.
AB - Interactions between T cell precursors and thymic stromal cells are essential during thymocyte development. However, the role of the thymus in initial commitment of lymphoid progenitors to the T lineage remains controversial, with data providing evidence for both extra- and intrathymic commitment mechanisms. In this context, it is clear that Notch1 is an important mediator during initiation of T cell development. Here we have analyzed the mechanisms regulating Notch activation in lymphoid precursors at extrathymic sites and in the thymus, including stages representing the first wave of embryonic thymus colonization on embryonic day 12 of gestation. We show that Notch activation in migrant lymphoid precursors requires entry into the thymic microenvironment where they are exposed to Notch ligands expressed by immature thymic epithelial cells. Moreover, continued Notch signaling in such precursors requires sustained interactions with Notch ligands. Collectively, these findings suggest a role for Notch in an intrathymic mechanism of T cell lineage commitment involving sustained interactions with Notch ligand bearing thymic epithelium.
M3 - Article
C2 - 12538689
VL - 170
SP - 1299
EP - 1303
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 3
ER -