Notch Signalling Regulates Cytokine Production by CD8+ and CD4+ T Cells

• Published in: Scandinavian journal of immunology 2012-04, Vol.75 (4), p.389-400
• Main Authors: Sauma, D., Ramirez, A., Alvarez, K., Rosemblatt, M., Bono, M. R.
• Format: Article
• Language: English
• Subjects: Animals; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell activation; Cells, Cultured; Coculture Techniques; Cytokines; Cytokines - biosynthesis; Cytokines - immunology; Differentiation; gamma -Interferon; Interleukin 10; Interleukin 17; Lymphocytes T; Mice; Mice, Inbred C57BL; Notch protein; Receptor mechanisms; Receptors, Notch - immunology; Receptors, Notch - metabolism; Secretase; Signal Transduction; Thymus Gland - immunology
• ISSN: 0300-9475; 1365-3083
• 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.