title: T cell-dependent activation of dendritic cells requires IL-12 and IFN-gamma signaling in T cells.
abstract: Patients presenting with genetic deficiencies in IFNGR1, IFNGR2, IL-12B, and IL-12RB1 display increased susceptibility to mycobacterial infections. We analyzed in this group of patients the cross-talk between human CD4+ T lymphocytes and dendritic cells (DCs) that leads to maturation of DC into producers of bioactive IL-12 and to activation of T cells into IFN-gamma producers. We found that this cross-talk is defective in all patients from this group. Unraveling the mechanisms underlying this deficiency, we showed that IL-12 signaling in T cells is required to induce expression of costimulatory molecules and secretion of IL-12 by DCs and that IFNGR expression is required on both DCs and CD4+ T cells to induce IL-12 secretion by DCs. These data suggest that CD4+ T cell-mediated activation of DCs plays a critical role in the defense against mycobacterial infections in humans.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 653, Institut Curie, Paris, France.
authors.forename: Francesc
authors.initials: F
authors.lastname: Miro
authors.forename: Cinzia
authors.initials: C
authors.lastname: Nobile
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blanchard
authors.forename: Marianne
authors.initials: M
authors.lastname: Lind
authors.forename: Orchidée
authors.initials: O
authors.lastname: Filipe-Santos
authors.forename: Claire
authors.initials: C
authors.lastname: Fieschi
authors.forename: Ariane
authors.initials: A
authors.lastname: Chapgier
authors.forename: Guillaume
authors.initials: G
authors.lastname: Vogt
authors.forename: Ludovic
authors.initials: L
authors.lastname: de Beaucoudrey
authors.forename: Dinakantha S
authors.initials: DS
authors.lastname: Kumararatne
authors.forename: Françoise
authors.initials: F
authors.lastname: Le Deist
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.forename: Sebastian
authors.initials: S
authors.lastname: Amigorena
authors.forename: Claire
authors.initials: C
authors.lastname: Hivroz
mesh_terms: D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D018664:Interleukin-12 / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D018089:Superantigens / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018089:Superantigens; D018664:Interleukin-12; D007371:Interferon-gamma