| First Author | Laky K | Year | 2015 |
| Journal | Immunity | Volume | 42 |
| Issue | 1 | Pages | 80-94 |
| PubMed ID | 25607460 | Mgi Jnum | J:260576 |
| Mgi Id | MGI:6142576 | Doi | 10.1016/j.immuni.2014.12.027 |
| Citation | Laky K, et al. (2015) Notch signaling regulates antigen sensitivity of naive CD4+ T cells by tuning co-stimulation. Immunity 42(1):80-94 |
| abstractText | 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. |
