The Transcription Factor Foxo1 Controls Central-Memory CD8+ T Cell Responses to Infection

•Foxo1 controls memory CD8+ T cell responses to infection•MPECs express higher amounts of Foxo1 than do SLECs•Foxo1 regulates the differentiation and homeostasis of MPECs•Memory-T-cell-promoting molecules Tcf7 and Ccr7 are Foxo1-bound target genes

SummaryMemory T cells protect hosts from pathogen reinfection, but how these cells emerge from a pool of antigen-experienced T cells is unclear. Here, we show that mice lacking the transcription factor Foxo1 in activated CD8+ T cells have defective secondary, but not primary, responses to Listeria monocytogenes infection. Compared to short-lived effector T cells, memory-precursor T cells expressed higher amounts of Foxo1, which promoted their generation and maintenance. Chromatin immunoprecipitation sequencing revealed the transcription factor Tcf7 and the chemokine receptor Ccr7 as Foxo1-bound target genes, which have critical functions in central-memory T cell differentiation and trafficking. These findings demonstrate that Foxo1 is selectively incorporated into the genetic program that regulates memory CD8+ T cell responses to infection.

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