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Production in Peripheral T Cells 1
* Department of Veterinary & Animal Sciences, University of Massachusetts, Amherst, MA 01003;
Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois, Chicago, IL 60612; and
Departments of Neuroscience and Pharmacology, Mayo Clinic, Jacksonville, FL 32224
Notch genes encode membrane receptors that regulate cell fate decisions in metazoa. Notch receptors and ligands are expressed in developing lymphoid tissue and mature lymphocytes and the role of Notch signaling in early T and B cell development has been studied extensively. However, its contribution to mature T cell function is unknown. TCR-mediated T cell activation is a fundamental process of the adaptive immune system that has been studied for decades; however, the details of this process are incompletely understood. In this study, we present evidence that Notch is required for TCR-mediated activation of peripheral T cells. Inhibition of Notch activation dramatically decreases T cell proliferation in both CD4 and CD8 cells and blocks both NF-
B activity and IFN-
production in peripheral T cells. Our data reveal a new, nondevelopmental function of Notch as a previously unknown key link in peripheral T cell activation and cytokine secretion.
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