Published online April 21, 2008
doi:10.1083/jcb.1813rr3
The Journal of Cell Biology, Vol. 181, No. 3, 401-
The Rockefeller University Press, 0021-9525 $30.00
© 2008 LeBrasseur
mTOR sends T cells on their way
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More T cells remain in lymph nodes instead of exploring the body in mice when the mTOR/PI3K pathway is blocked (right).
CANTRELL/MACMILLAN
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Only well-fed T cells explore the body for intruders, if results from Linda Sinclair, Doreen Cantrell (University of Dundee, Scotland), and colleagues are any indication. T cell trafficking, the group finds, is linked to nutrient-sensing pathways.
The group connected nutrient status with trafficking when they noticed that stimuli that decrease T cells' cache of nutrient receptors boost levels of CCR7 and L-selectin, which help keep T cells in lymph nodes. When nutrients are plentiful, metabolism is dialed up by the mTOR/PI3K pathway, which the group now shows reduces L-selectin levels via two routes.
In one route, PI3K and its PIP3 lipid product led to the rapid cleavage of L-selectin on the T cell surface. A later-acting path prevented the transcription of CCR7 and new L-selectin.
L-selectin and CCR7 levels are normally turned down when T cells are activated by antigen in the lymph nodes. The loss allows foreigner-fighting T cells to leave the node and head to remote tissues. The new results suggest that this exit does not occur in starved cells, which cannot turn on mTOR; inhibiting mTOR/PI3K in mouse cells restored L-selectin levels and retained T cells in lymph nodes.
"The system ensures that a T cell does not leave the node," says Cantrell, "until it is in a metabolic state to do its job. It's like explorers making a dash for the North Pole. They need to be well fed before they go. And if they're not, they should return to base camp." 
Sinclair, L.V., et al. 2008. Nat. Immunol. doi:10.1038/ni.1603.
Nicole LeBrasseur
lebrasn{at}rockefeller.edu
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