Journal
CELL
Volume 166, Issue 4, Pages 977-990Publisher
CELL PRESS
DOI: 10.1016/j.cell.2016.07.006
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Funding
- NIH [R37 AI034206, P30 CA008748, U01 HG007893]
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Eukaryotic cells can remember'' transient encounters with a wide range of stimuli, inducing lasting states of altered responsiveness. Regulatory T (Treg) cells are a specialized lineage of suppressive CD4 T cells that act as critical negative regulators of inflammation in various biological contexts. Treg cells exposed to inflammatory conditions acquire strongly enhanced suppressive function. Using inducible genetic tracing, we analyzed the long-term stability of activation-induced transcriptional, epigenomic, and functional changes in Treg cells. We found that the inflammation-experienced Treg cell population reversed many activation-induced changes and lost its enhanced suppressive function over time. The memory-less'' potentiation of Treg suppressor function may help avoid a state of generalized immunosuppression that could otherwise result from repeated activation.
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