The transcription factor Foxo1 controls central-memory CD8+ T cell responses to infection.
Memory 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.
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Myoungjoo V
MV
Kim
Weiming
W
Ouyang
Will
W
Liao
Michael Q
MQ
Zhang
Ming O
MO
Li
D019264:Adoptive Transfer; D000818:Animals; D001854:Bone Marrow Cells; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics; D051538:Hepatocyte Nuclear Factor 1-alpha; D007156:Immunologic Memory / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D054400:Receptors, CCR7 / Q000378:metabolism*; D051822:T Cell Transcription Factor 1 / Q000378:metabolism*
C515371:Ccr7 protein, mouse; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D054400:Receptors, CCR7; D051822:T Cell Transcription Factor 1; D049452:Green Fluorescent Proteins