Notch 1 signaling regulates peripheral T cell activation

Todd N. Eagar, Qizhi Tang, Michael Wolfe, Yiping He, Warren S. Pear, Jeffrey A. Bluestone

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

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 GSK3β 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.

Original languageEnglish (US)
Pages (from-to)407-415
Number of pages9
JournalImmunity
Volume20
Issue number4
DOIs
StatePublished - Apr 1 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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    Eagar, T. N., Tang, Q., Wolfe, M., He, Y., Pear, W. S., & Bluestone, J. A. (2004). Notch 1 signaling regulates peripheral T cell activation. Immunity, 20(4), 407-415. https://doi.org/10.1016/S1074-7613(04)00081-0