Transcription Factor Foxo1 Controls Memory CD8+ T Cell Responses To Infection [ChIP-Seq]
Memory T cells provide immunity against pathogen reinvasion, but mechanisms of their long-term maintenance is unclear.  Here we show that mice with the deletion of the transcription factor Foxo1 in activated CD8+ T cells had defective secondary but not primary responses to Listeria monocytogenes infection.  Compared to short-lived effector T cells, memory precursor effector T cells expressed higher amounts of Foxo1 that promoted their generation and maintenance.  Gene expression profiling and chromatin immunoprecipitation sequencing experiments revealed the chemokine receptor CCR7 and the transcription factor TCF1 as novel Foxo1-bound target genes with critical functions in memory T cell trafficking and transcriptional regulation.  These findings demonstrate that Foxo1 is selectively incorporated into the genetic program that regulates memory but not effector CD8+ T cell responses to infection. Overall design: CD8+ T cells were isolated from wild-type or Foxo1tagBirA mice in which Foxo1 is endogenously biotinylated. Foxo1 binding targets in CD8+ cells were identified by using Foxo1 antibody- and Streptavidin- ChIP-Seq approaches.