Abstract
Migration of dendritic cells (DCs) to the draining lymph node (DLN) is required for the activation of naive T cells. We show here that migration of DCs from the lung to the DLN after Mycobacterium tuberculosis (Mtb) exposure is defective in mice lacking interleukin (IL)-12p40. This defect compromises the ability of IL-12p40-deficient DCs to activate naive T cells in vivo; however, DCs that express IL-12p40 alone can activate naive T cells. Treatment of IL-12p40-deficient DCs with IL-12p40 homodimer (IL-12(p40)(2)) restores Mtb-induced DC migration and the ability of IL-12p40-deficient DCs to activate naive T cells. These data define a novel and fundamental role for IL-12p40 in the pathogen-induced activation of pulmonary DCs.
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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Animals
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CD4-Positive T-Lymphocytes / immunology*
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Cell Movement / immunology*
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Cells, Cultured
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Dendritic Cells / cytology*
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Interleukin-12 / deficiency
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Interleukin-12 / genetics
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Interleukin-12 / physiology*
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Interleukin-12 Subunit p40
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Lymph Nodes / cytology
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Lymph Nodes / 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, Knockout
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Mycobacterium tuberculosis / immunology*
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Protein Subunits / deficiency
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Protein Subunits / genetics
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Protein Subunits / physiology*
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Tuberculosis, Pulmonary / immunology*
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Tuberculosis, Pulmonary / microbiology
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Tuberculosis, Pulmonary / pathology
Substances
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Interleukin-12 Subunit p40
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Protein Subunits
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Interleukin-12