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J Exp Med ; 203(7): 1805-15, 2006 Jul 10.
Article in English | MEDLINE | ID: mdl-16818672

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.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Cell Movement/immunology , Dendritic Cells/cytology , Dendritic Cells/immunology , Interleukin-12/physiology , Lymphocyte Activation/immunology , Mycobacterium tuberculosis/immunology , Protein Subunits/physiology , Tuberculosis, Pulmonary/immunology , Animals , Cells, Cultured , Dendritic Cells/metabolism , Interleukin-12/deficiency , Interleukin-12/genetics , Interleukin-12 Subunit p40 , Lymph Nodes/cytology , Lymph Nodes/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Protein Subunits/deficiency , Protein Subunits/genetics , Tuberculosis, Pulmonary/microbiology , Tuberculosis, Pulmonary/pathology
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