Interleukin 12 – dependent Interferon g Production by CD 8 a 1 Lymphoid Dendritic Cells

We investigated the role of antigen-presenting cells in early interferon (IFN)g production in normal and recombinase activating gene 2–deficient (Rag-2 2/2 ) mice in response to Listeria monocytogenes (LM) infection and interleukin (IL)-12 administration. Levels of serum IFNg in Rag-2 2/2 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 IFNg levels in the sera of Rag-2 2/2 mice after LM infection or IL-12 injection. Incubation of splenocytes from NK cell–depleted Rag-2 2/2 mice with LM resulted in the production of IFNg that was completely blocked by addition of anti–IL-12 antibodies. Both dendritic cells (DCs) and monocytes purified from splenocytes were capable of producing IFNg when cultured in the presence of IL-12. Intracellular immunofluorescence analysis confirmed the IFNg production from DCs. It was further shown that IFNg was produced predominantly by CD8 a 1 lymphoid DCs rather than CD8 a 2 myeloid DCs. Collectively, our data indicated that DCs are potent in producing IFNg 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.