Institut Pasteur, Dynamics of Immune Responses Unit, Paris, France.
PLoS One. 2011 Apr 28;6(4):e18916. doi: 10.1371/journal.pone.0018916.
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.
T 细胞通常会在淋巴结中与多个 DC 进行连续接触，并且很可能配备了允许它们对连续接收到的信号进行求和的机制。我们发现，即使在数小时后进行二次刺激，短至两小时的刺激期也可以在 T 细胞上留下该激活信号的“生化记忆”，持续数小时。这可以通过更快地诱导激活标志物和更早地承诺进行增殖来证明，即使在随后的刺激发生数小时后也是如此。瞬时早期基因产物 c-fos 的上调，即 AP-1 转录因子的组成部分，在刺激后 1-2 小时达到最大值，并且在刺激消退后数小时内蛋白水平仍保持升高。此外，稳定且转录活跃的磷酸化 c-fos 形式至少持续一天。在体内进行短暂的抗原刺激后，我们还观察到 c-fos 的快速上调，随后的刺激可以增强这种上调。因此，磷酸化 c-fos 的积累可能是先前亚最佳刺激的生化指纹，使 T 细胞在下次遇到携带抗原的 DC 时能够迅速恢复其激活程序。
