Notch signaling augments T cell responsiveness by enhancing CD25 expression.
Notch receptors signal through a highly conserved pathway to influence cell fate decisions. Notch1 is required for T lineage commitment; however, a role for Notch signaling has not been clearly defined for the peripheral T cell response. Notch gene expression is induced, and Notch1 is activated in primary CD4(+) T cells following specific peptide-Ag stimulation. Notch activity contributes to the peripheral T cell response, as inhibition of endogenous Notch activation decreases the proliferation of activated T cells in a manner associated with the diminished production of IL-2 and the expression of the high affinity IL-2R (CD25). Conversely, forced expression of a constitutively active Notch1 in primary T cells results in increased surface expression of CD25, and renders these cells more sensitive to both cognate Ag and IL-2, as measured by cell division. These data suggest an important role for Notch signaling during CD4(+) T cell responses, which operates through augmenting a positive feedback loop involving IL-2 and its high affinity receptor.
Adler
Scott H
SH
Departments of Medicine, Institute for Medicine and Engineering, The Abramson Family Cancer Research Institute, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA.
Chiffoleau
Elise
E
Xu
Lanwei
L
Dalton
Nicole M
NM
Burg
Jennifer M
JM
Wells
Andrew D
AD
Wolfe
Michael S
MS
Turka
Laurence A
LA
Pear
Warren S
WS
D000276:Adjuvants, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002462:Cell Membrane / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D007376:Interleukin-2 / Q000494:pharmacology; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis* / Q000502:physiology; D051880:Receptors, Notch; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D014157:Transcription Factors; D014161:Transduction, Genetic; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology*
D000276:Adjuvants, Immunologic; D006131:Growth Inhibitors; D007376:Interleukin-2; D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D011956:Receptors, Cell Surface; D015375:Receptors, Interleukin-2; D051880:Receptors, Notch; D014157:Transcription Factors