Notch 1 signaling regulates peripheral T cell activation.

Journal Article (Journal Article)

Notch signaling has been identified as an important regulator of leukocyte differentiation and thymic maturation. Less is known about the role of Notch signaling in regulating mature T cells. We examined the role of Notch 1 in regulating peripheral T cell activity in vitro and in vivo. Coligation of Notch 1 together with TCR and CD28 resulted in a dramatic inhibition of T cell activation, proliferation, and cytokine production. This effect was dependent on presenilin activity and induced the expression of HES-1, suggestive of Notch 1 signaling. Biochemical analysis demonstrated an inhibition of AKT and GSK3beta phosphorylation following Notch 1 engagement while other biochemical signals such as TCR and ERK phosphorylation remained intact. Similar effects were observed in vivo in an adoptive transfer model. Therefore, Notch 1 signaling may play an important role in regulating naive T cell activation and homeostasis.

Full Text

Duke Authors

Cited Authors

  • Eagar, TN; Tang, Q; Wolfe, M; He, Y; Pear, WS; Bluestone, JA

Published Date

  • April 2004

Published In

Volume / Issue

  • 20 / 4

Start / End Page

  • 407 - 415

PubMed ID

  • 15084270

International Standard Serial Number (ISSN)

  • 1074-7613

Digital Object Identifier (DOI)

  • 10.1016/s1074-7613(04)00081-0


  • eng

Conference Location

  • United States