Notch and the survival of regulatory T cells: location is everything!

TitleNotch and the survival of regulatory T cells: location is everything!
Publication TypeJournal Article
Year of Publication2012
AuthorsMinter LM, Osborne BA
JournalScience signaling
Volume5
Issue234
Paginationpe31
Date Published2012
ISSN1937-9145
AbstractSignaling through the T cell receptor induces T lymphocytes to divide, differentiate, and perform numerous effector functions. Once activated, effector T cells are exquisitely sensitive to changes in available cytokines, particularly the survival cytokine interleukin-2 (IL-2). Removal of IL-2 rapidly initiates apoptosis in response to cytokine withdrawal. In contrast to effector T cells, regulatory T cells (T(regs)) are resistant to apoptosis induced by cytokine withdrawal. A study exploring the differences between these two T cell subsets reveals a role for Notch1 in protecting T(regs) from apoptosis. Protection from apoptosis induced by cytokine withdrawal correlated with Notch1 localization in the cytosol of T(regs) and its association with phosphatidylinositol 3-kinase and Rictor, a component of the mammalian target of rapamycin complex. Notch1 localization in the nucleus in effector T cells, on the other hand, was correlated with susceptibility to apoptosis induced by cytokine withdrawal. This study highlights how Notch1 can deliver opposing signals in different cellular contexts and suggests that localization of Notch1 can have a substantial influence on life-and-death decisions in T lymphocytes.
DOI10.1126/scisignal.2003358
Alternate JournalSci Signal
PubMed ID22827995