Research ArticleImmunology

Distinct Spatial and Molecular Features of Notch Pathway Assembly in Regulatory T Cells

Sci. Signal.  24 Jul 2012:
Vol. 5, Issue 234, pp. ra53
DOI: 10.1126/scisignal.2002859

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Cytosolic Notch Protects T Cells

Effector T cells direct the immune response against pathogens, whereas regulatory T cells (Tregs) suppress effector T cell function to keep the immune response in check. In addition to their opposing functions, these cells have different responses when survival cytokines are unavailable. Effector T cells undergo apoptosis, whereas Tregs survive (see the Perspective by Minter and Osborne). Perumalsamy et al. found that the differential survival of effector T cells and Tregs correlated with differential signaling by the receptor Notch1. Whereas the Notch1 intracellular domain (NICD) was localized to the nucleus in effector T cells, it was localized in the cytosol of Tregs, and blockade of Notch1 signaling or prevention of the cytosolic localization of NICD abolished the protection of Tregs from apoptosis. Treg survival depended on interactions between Notch1 and components of the phosphatidylinositol 3-kinase and mammalian target of rapamycin signaling pathways. Together, these data implicate spatial control of Notch signaling components in the protection of specific T cell subsets from apoptosis.