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

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. The mechanisms underlying the heightened protection mediated by central memory CD8(+) T (T-CM) cells remain unclear. Here we show that the transcription factor Tcf1 was required in resting T-CM cells to generate secondary effector CD8(+) T cells and to clear pathogens during recall responses. Recall stimulation of CD8(+) T-CM 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(+) T-CM cells, but depended on Tcf1 for optimal induction and chromatin opening in recall-stimulated CD8(+) T-CM cells. Tcf1 bound extensively to these recall-induced gene loci in resting CD8(+) T-CM 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(+) T-CM cells in case of a secondary challenge.

Automated summary

Xue and colleagues demonstrate that the transcription factor Tcf1 plays a vital role in preprogramming the transcriptional program of CD8(+) central memory T cells, providing the necessary bioenergetic and proliferative support during secondary challenges. Tcf1 is required for the generation of secondary effector CD8(+) T cells and pathogen clearance during recall responses. Additionally, Tcf1 mediates extensive chromatin interactions and facilitates the induction of important genes in recall-stimulated CD8(+) T-CM cells.