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Notch controls generation and function of human effector CD8+ T cells
- Source :
- Blood; April 2013, Vol. 121 Issue: 14 p2638-2646, 9p
- Publication Year :
- 2013
-
Abstract
- The generation of effector CD8+ T cells with lytic capacity is crucial for tumor control. Dendritic cells (DCs) provide important signals to promote naive CD8+ T cell priming and activation of effector T cells. Here, we report that the Notch pathway has an important role in both these processes in human CD8+ T cells. Activated monocyte-derived DCs express Notch ligands Jagged1 and Delta-like4, whereas naive CD8+ T cells express Notch2. The role for Notch signaling in CD8+ T cell priming was determined using an ex-vivo model system in which tumor antigen–specific primary CD8+ T cell responses were measured. Inhibition of Notch using γ-secretase inhibitors or soluble Delta-like4-Fc during activation reduced expansion of antigen-specific CD8+ T cells, which was mirrored by decreased frequencies of interferon (IFN)γ-, tumor necrosis factor-α–, and granzymeB-producing CD8+ T cells. Moreover, T cells primed when Notch signaling was prevented are functionally low-avidity T cells. In addition, Notch partially regulates established effector T cell function. Activation-induced Notch signaling is needed for IFNγ release but not for cytolytic activity. These data indicate that Notch signaling controls human CD8+ T cell priming and also influences effector T cell functions. This may provide important information for designing new immunotherapies for treatment of cancer.
Details
- Language :
- English
- ISSN :
- 00064971 and 15280020
- Volume :
- 121
- Issue :
- 14
- Database :
- Supplemental Index
- Journal :
- Blood
- Publication Type :
- Periodical
- Accession number :
- ejs30086760
- Full Text :
- https://doi.org/10.1182/blood-2012-07-442962