美国哈肯萨克大学Hai-Hui Xue、弗吉尼亚大学Chongzhi Zang等研究人员合作发现，Tcf1在回忆应答期间调节中央记忆CD8⁺ T细胞糖酵解功能的动员。相关论文于2022年2月21日在线发表在《自然—免疫学》杂志上。

研究人员发现，转录因子Tcf1需要在静止的中央记忆CD8⁺ T（T_CM）细胞中产生二级效应CD8⁺ T细胞，并在回忆应答中清除病原体。对CD8⁺ T_CM细胞的召回刺激引起了转录组和染色质可及性的广泛重编程，导致糖酵解酶、细胞周期调节器和转录调节器的快速诱导，包括Id3。这组基因在静止的CD8⁺ T_CM细胞中不需要Tcf1，但在召回刺激的CD8⁺ T_CM细胞中则需要依赖Tcf1进行最佳诱导和染色质开放。Tcf1在静止的CD8⁺ T_CM细胞中广泛地与这些召回诱导的基因位点结合，并介导染色质相互作用，使这些基因与准备好的增强子在结构上接近。因此，Tcf1预设了一个转录程序，支持CD8⁺ T_CM细胞在二次感染时的生物能量和增殖需要。

据介绍，T_CM细胞介导高度保护的机制仍不清楚。

附：英文原文

Title: Tcf1 preprograms the mobilization of glycolysis in central memory CD8+ T cells during recall responses

Author: Shan, Qiang, Hu, Shengen Shawn, Zhu, Shaoqi, Chen, Xia, Badovinac, Vladimir P., Peng, Weiqun, Zang, Chongzhi, Xue, Hai-Hui

Issue&Volume: 2022-02-21

Abstract: The mechanisms underlying the heightened protection mediated by central memory CD8+ T (TCM) cells remain unclear. Here we show that the transcription factor Tcf1 was required in resting TCM cells to generate secondary effector CD8+ T cells and to clear pathogens during recall responses. Recall stimulation of CD8+ TCM cells caused extensive reprogramming of the transcriptome and chromatin accessibility, leading to rapid induction of glycolytic enzymes, cell cycle regulators and transcriptional regulators, including Id3. This cluster of genes did not require Tcf1 in resting CD8+ TCM cells, but depended on Tcf1 for optimal induction and chromatin opening in recall-stimulated CD8+ TCM cells. Tcf1 bound extensively to these recall-induced gene loci in resting CD8+ TCM cells and mediated chromatin interactions that positioned these genes in architectural proximity with poised enhancers. Thus, Tcf1 preprogramed a transcriptional program that supported the bioenergetic and proliferative needs of CD8+ TCM cells in case of a secondary challenge. Xue and colleagues show that the transcription factor Tcf1 preprograms a transcriptional program that supports the bioenergetic and proliferative needs of CD8+ central memory T cells in case of a secondary challenge.

DOI: 10.1038/s41590-022-01131-3

Source: https://www.nature.com/articles/s41590-022-01131-3