T cell-dependent activation of dendritic cells requires IL-12 and IFN-gamma signaling in T cells.
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.
Miro
Francesc
F
Institut National de la Santé et de la Recherche Médicale Unité 653, Institut Curie, Paris, France.
Nobile
Cinzia
C
Blanchard
Nicolas
N
Lind
Marianne
M
Filipe-Santos
Orchidée
O
Fieschi
Claire
C
Chapgier
Ariane
A
Vogt
Guillaume
G
de Beaucoudrey
Ludovic
L
Kumararatne
Dinakantha S
DS
Le Deist
Françoise
F
Casanova
Jean-Laurent
JL
Amigorena
Sebastian
S
Hivroz
Claire
C
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*
D018089:Superantigens; D018664:Interleukin-12; D007371:Interferon-gamma