[PDF][PDF] Notch signaling regulates antigen sensitivity of naive CD4+ T cells by tuning co-stimulation

K Laky, S Evans, A Perez-Diez, BJ Fowlkes - Immunity, 2015 - cell.com
K Laky, S Evans, A Perez-Diez, BJ Fowlkes
Immunity, 2015cell.com
Adaptive immune responses begin when naive CD4+ T cells engage peptide+ major
histocompatibility complex class II and co-stimulatory molecules on antigen-presenting cells
(APCs). Notch signaling can influence effector functions in differentiated CD4+ T helper and
T regulatory cells. Whether and how ligand-induced Notch signaling influences the initial
priming of CD4+ T cells has not been addressed. We have found that Delta Like Ligand 4
(DLL4)-induced Notch signaling potentiates phosphatidylinositol 3-OH kinase (PI3K) …
Summary
Adaptive immune responses begin when naive CD4+ T cells engage peptide+major histocompatibility complex class II and co-stimulatory molecules on antigen-presenting cells (APCs). Notch signaling can influence effector functions in differentiated CD4+ T helper and T regulatory cells. Whether and how ligand-induced Notch signaling influences the initial priming of CD4+ T cells has not been addressed. We have found that Delta Like Ligand 4 (DLL4)-induced Notch signaling potentiates phosphatidylinositol 3-OH kinase (PI3K)-dependent signaling downstream of the T cell receptor+CD28, allowing naive CD4+ T cells to respond to lower doses of antigen. In vitro, DLL4-deficient APCs were less efficient stimulators of CD4+ T cell activation, metabolism, proliferation, and cytokine secretion. With deletion of DLL4 from CD11c+ APCs in vivo, these deficits translated to an impaired ability to mount an effective CD4+-dependent anti-tumor response. These data implicate Notch signaling as an important regulator of adaptive immune responses.
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