Immunity
Volume 20, Issue 5, May 2004, Pages 611-622
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Article
Regulation of αβ/γδ T Cell Lineage Commitment and Peripheral T Cell Responses by Notch/RBP-J Signaling

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Abstract

RBP-J is a key mediator of Notch signaling that regulates a large spectrum of cell fate determinations. To elucidate the functions of Notch signaling in T cell development, we inactivated RBP-J specifically at two stages of T cell development by crossing RBP-J floxed mice with lck-cre or CD4-cre transgenic mice. The loss of RBP-J at an earlier developmental stage resulted in enhanced generation and accelerated emigration of γδ T cells, whereas αβ T cell development was arrested at the double-negative 3 stage. The loss of RBP-J at a later stage did not affect the absolute number or the production rate of CD4 or CD8-positive mature T cells but enhanced Th1 cell response and reduced CD4+ T cell proliferation. Our data demonstrated that Notch/RBP-J signaling regulates γδ T cell generation and migration, αβ T cell maturation, terminal differentiation of CD4+ T cells into Th1/Th2 cells, and activation of T cells.

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These authors contributed equally to this work.