Notch 1 signaling regulates peripheral T cell activation

Immunity. 2004 Apr;20(4):407-15. doi: 10.1016/s1074-7613(04)00081-0.

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 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Blotting, Western
  • CD28 Antigens / immunology
  • CD28 Antigens / metabolism
  • Cell Division
  • Cell Line
  • Flow Cytometry
  • Humans
  • Lymphocyte Activation / immunology*
  • Mice
  • Precipitin Tests
  • Receptor, Notch1
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Cell Surface / immunology*
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • Transcription Factors*
  • Transfection

Substances

  • CD28 Antigens
  • NOTCH1 protein, human
  • Notch1 protein, mouse
  • Receptor, Notch1
  • Receptors, Antigen, T-Cell
  • Receptors, Cell Surface
  • Transcription Factors