Interleukin 12-dependent interferon gamma production by CD8 alpha(+) lymphoid dendritic cells

We investigated the role of antigen-presenting cells in early interferon (I FN)-gamma production in normal and recombinase activating gene 2-deficient (Rag-2(-/-)) mice in response to Listeria inmonocytogenes (LM) infection an d interleukin (IL)-12 administration. Levels of serum IFN-gamma in 'Rag-2(- /-) mice were comparable to those of normal mice upon either LM infection o r 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 o f 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 sple nocytes were capable of producing IFN-gamma when cultured in the presence o f IL-12. Intracellular immunofluorescence analysis confirmed the IFN-gamma production from DCs. It was further shown that IFN-gamma was produced predo minantly by CD8 alpha(+) lymphoid DCs rather than CD8 alpha(-) myeloid DCs. Collectively, our data indicated that DCs are potent in producing IFN-gamm a in response to IL-12 produced by bacterial infection and play an importan t role in innate immunity and subsequent T helper cell type 1 development i n vivo.