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Publication : A role for the immediate early gene product c-fos in imprinting T cells with short-term memory for signal summation.

First Author  Clark CE Year  2011
Journal  PLoS One Volume  6
Issue  4 Pages  e18916
PubMed ID  21552553 Mgi Jnum  J:172358
Mgi Id  MGI:5007556 Doi  10.1371/journal.pone.0018916
Citation  Clark CE, et al. (2011) A Role for the Immediate Early Gene Product c-fos in Imprinting T Cells with Short-Term Memory for Signal Summation. PLoS One 6(4):e18916
abstractText  T cells often make sequential contacts with multiple DCs in the lymph nodes and are likely to be equipped with mechanisms that allow them to sum up the successive signals received. We found that a period of stimulation as short as two hours could imprint on a T cell a 'biochemical memory' of that activation signal that persisted for several hours. This was evidenced by more rapid induction of activation markers and earlier commitment to proliferation upon subsequent stimulation, even when that secondary stimulation occurred hours later. Upregulation of the immediate early gene product c-fos, a component of the AP-1 transcription factor, was maximal by 1-2 hours of stimulation, and protein levels remained elevated for several hours after stimulus withdrawal. Moreover, phosphorylated forms of c-fos that are stable and transcriptionally active persisted for a least a day. Upon brief antigenic stimulation in vivo, we also observed a rapid upregulation of c-fos that could be boosted by subsequent stimulation. Accumulation of phosphorylated c-fos may therefore serve as a biochemical fingerprint of previous suboptimal stimulation, leaving the T cell poised to rapidly resume its activation program upon its next encounter with an antigen-bearing DC.
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