Interleukin 12-dependent interferon gamma production by CD8alpha+ lymphoid dendritic cells.
We investigated the role of antigen-presenting cells in early interferon (IFN)-gamma production in normal and recombinase activating gene 2-deficient (Rag-2(-/-)) mice in response to Listeria monocytogenes (LM) infection and interleukin (IL)-12 administration. Levels of serum IFN-gamma in Rag-2(-/-) mice were comparable to those of normal mice upon either LM infection or IL-12 injection. Depletion of natural killer (NK) cells by administration of anti-asialoGM1 antibodies had little effect on IFN-gamma levels in the sera of Rag-2(-/-) mice after LM infection or IL-12 injection. Incubation of splenocytes from NK cell-depleted Rag-2(-/-) mice with LM resulted in the production of IFN-gamma that was completely blocked by addition of anti-IL-12 antibodies. Both dendritic cells (DCs) and monocytes purified from splenocytes were capable of producing IFN-gamma when cultured in the presence of IL-12. Intracellular immunofluorescence analysis confirmed the IFN-gamma production from DCs. It was further shown that IFN-gamma was produced predominantly by CD8alpha+ lymphoid DCs rather than CD8alpha- myeloid DCs. Collectively, our data indicated that DCs are potent in producing IFN-gamma in response to IL-12 produced by bacterial infection and play an important role in innate immunity and subsequent T helper cell type 1 development in vivo.
Ohteki
T
T
Department of Immunology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
Fukao
T
T
Suzue
K
K
Maki
C
C
Ito
M
M
Nakamura
M
M
Koyasu
S
S
D000818:Animals; D016827:CD8 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D007371:Interferon-gamma / Q000378:metabolism*; D018664:Interleukin-12 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology / Q000472:pathogenicity; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000276:immunology; D019895:Transposases / Q000235:genetics
D016827:CD8 Antigens; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; D018664:Interleukin-12; D007371:Interferon-gamma; D019895:Transposases