Notch signalling regulates cytokine production by CD8+ and CD4+ T cells

Scand J Immunol. 2012 Apr;75(4):389-400. doi: 10.1111/j.1365-3083.2012.02673.x.


The Notch signalling pathway regulates several aspects of cellular differentiation such as T lineage commitment and effector functions on peripheral T cells; however, there is limited information regarding Notch receptor expression on different T cell subsets and the putative role of the different receptors on T cell effector function. Here, we studied the protein expression of Notch receptors on murine T cells in vitro and in vivo and analysed the role of the Notch pathway in cytokine production by CD4+ and CD8+ T cells. We found that resting CD4+ and CD8+ T cells do not express Notch receptors, but they upregulate Notch 1 and Notch 2 shortly after in vitro and in vivo activation. Using a γ-secretase inhibitor, which blocks Notch signalling through all Notch receptors, we demonstrated that the Notch pathway regulates IL-10 production by CD4+ T cells and IFN-γ and IL-17 production by CD8+ T cells. These results suggest that Notch 1 and 2 are expressed by CD4+ and CD8+ T cells and represent the putative Notch receptors that regulate effector functions and cytokine production by these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Coculture Techniques
  • Cytokines / biosynthesis
  • Cytokines / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Receptors, Notch / immunology
  • Receptors, Notch / metabolism
  • Signal Transduction*
  • Thymus Gland / immunology


  • Cytokines
  • Receptors, Notch