Notch1 co-localizes with CD4 on activated T cells and Notch signaling is required for IL-10 production.
The effector function of activated CD4(+) T cells and secretion of cytokines are important in the establishment of productive immune responses and tolerance. We identified expression by CD4(+) T cells of Notch receptors and ligands and enhanced Notch signaling upon activation. Notch1 expression was up regulated and co-localized with CD4 upon T cell stimulation. Disruption of Notch signaling did not affect proliferation, but attenuated cytokine secretion following CD3 ligation in the absence of anti-CD28 antibody. Notch signaling was absolutely necessary for transcription of IL-10 by stimulated CD4(+) T cells. CD4(+) T cells transfected with constitutively active Notch1 failed to proliferate, but exhibited enhanced cytokine secretion upon stimulation. Our data indicates that Notch receptor signaling can influence both proliferative and cytokine responses of CD4(+) T cells. In addition, the finding that Notch signaling is required for production of IL-10 may allude to a role in immune regulation.
Benson
Robert A
RA
Immunobiology Group, Medical Research Council Centre for Inflammation Research, University of Edinburgh Medical School, Edinburgh, UK. rbenson@staffmail.ed.ac.uk
Adamson
Karen
K
Corsin-Jimenez
Marta
M
Marley
Julia V
JV
Wahl
Karen A
KA
Lamb
Jonathan R
JR
Howie
Sarah E M
SE
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D051880:Receptors, Notch; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D014162:Transfection
D015704:CD4 Antigens; D016207:Cytokines; D008565:Membrane Proteins; D051880:Receptors, Notch; D016753:Interleukin-10