Abstract
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.
Copyright © 2013 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Bone Marrow Cells
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Differentiation
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Forkhead Box Protein O1
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Forkhead Transcription Factors / deficiency
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism*
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Green Fluorescent Proteins / genetics
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Hepatocyte Nuclear Factor 1-alpha
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Immunologic Memory / immunology*
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Listeria monocytogenes / immunology
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Listeriosis / immunology
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Receptors, CCR7 / metabolism*
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T Cell Transcription Factor 1 / metabolism*
Substances
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Ccr7 protein, mouse
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Foxo1 protein, mouse
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Hepatocyte Nuclear Factor 1-alpha
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Hnf1a protein, mouse
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Receptors, CCR7
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T Cell Transcription Factor 1
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Green Fluorescent Proteins