Notch 1 signaling regulates peripheral T cell activation.
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.
Eagar
Todd N
TN
Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 USA.
Tang
Qizhi
Q
Wolfe
Michael
M
He
Yiping
Y
Pear
Warren S
WS
Bluestone
Jeffrey A
JA
D019264:Adoptive Transfer; D000818:Animals; D015153:Blotting, Western; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D011233:Precipitin Tests; D051881:Receptor, Notch1; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors; D014162:Transfection
D018106:CD28 Antigens; C497761:NOTCH1 protein, human; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; D014157:Transcription Factors