title: Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection.
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.
authors.affiliation: Trudeau Institute, Inc., Saranac Lake, NY 12983, USA.
authors.forename: Shabaana A
authors.initials: SA
authors.lastname: Khader
authors.forename: Santiago
authors.initials: S
authors.lastname: Partida-Sanchez
authors.forename: Guy
authors.initials: G
authors.lastname: Bell
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Jelley-Gibbs
authors.forename: Susan
authors.initials: S
authors.lastname: Swain
authors.forename: John E
authors.initials: JE
authors.lastname: Pearl
authors.forename: Nico
authors.initials: N
authors.lastname: Ghilardi
authors.forename: Frederic J
authors.initials: FJ
authors.lastname: Desauvage
authors.forename: Frances E
authors.initials: FE
authors.lastname: Lund
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Cooper
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D053762:Interleukin-12 Subunit p40; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D018664:Interleukin-12