Abstract
Interleukin 7 (IL-7) and T cell antigen receptor signals have been proposed to be the main drivers of homeostatic T cell proliferation. However, it is not known why CD4(+) T cells undergo less-efficient homeostatic proliferation than CD8(+) T cells do. Here we show that systemic IL-7 concentrations increased during lymphopenia because of diminished use of IL-7 but that IL-7 signaling on IL-7 receptor-alpha-positive (IL-7Ralpha(+)) dendritic cells (DCs) in lymphopenic settings paradoxically diminished the homeostatic proliferation of CD4(+) T cells. This effect was mediated at least in part by IL-7-mediated downregulation of the expression of major histocompatibility complex class II on IL-7Ralpha(+) DCs. Our results indicate that IL-7Ralpha(+) DCs are regulators of the peripheral CD4(+) T cell niche and that IL-7 signals in DCs prevent uncontrolled CD4(+) T cell population expansion in vivo.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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Cell Proliferation*
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Dendritic Cells / immunology
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Dendritic Cells / metabolism*
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Enzyme-Linked Immunosorbent Assay
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Feedback, Physiological
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Histocompatibility Antigens Class II / immunology
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Histocompatibility Antigens Class II / metabolism
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Homeostasis / immunology*
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Interleukin-7 / genetics
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Interleukin-7 / immunology
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Interleukin-7 / metabolism*
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Lymphocyte Activation / immunology
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Lymphopenia / immunology
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Lymphopenia / metabolism
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Mice
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Mice, Mutant Strains
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Receptors, Interleukin-7 / immunology
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Receptors, Interleukin-7 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / physiology
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Stromal Cells / immunology
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Stromal Cells / metabolism
Substances
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Histocompatibility Antigens Class II
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Interleukin-7
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Receptors, Interleukin-7