This study investigates the reciprocal activating interaction between human peripheral blood natural killer (NK) cells and monocyte-derived immature dendritic cells (DC). The results show that NK cells, when activated by IL-2 or by mature DC, enhance DC maturation and interleukin (IL)-12 production. Conversely, immature DC, when exposed to maturation stimuli such as LPS, Mycobacterium tuberculosis, or IFN-α, significantly enhance NK cell cytotoxicity and CD69 expression. The interaction is cell contact-dependent, although the secretion of IFN-γ and TNF also contributes to DC maturation. The reciprocal activating interaction was restricted to NK cells, as other lymphocyte subsets did not express CD69 or mature upon contact with DC. These findings demonstrate a bidirectional cross talk between NK cells and DC, where NK cells activated by IL-2 or by mature DC induce DC maturation. The study also shows that IL-2-activated NK cells directly induce DC maturation and enhance their ability to stimulate allogeneic naive CD4+ T cells. The effects of NK cells on DC maturation were found to depend on cell-to-cell contact, although the secretion of IFN-γ and TNF also contributed to DC maturation. The study highlights the importance of NK cells in the immune response, as they not only act as effector cells of innate resistance but also regulate adaptive immunity. The findings suggest that NK cells play a crucial role in the activation and maturation of DC, which in turn enhances the immune response. The study also indicates that the interaction between NK cells and DC is regulated to prevent unnecessary activation of self-reactive or bystander cells. The results suggest that the cross talk between NK cells and DC is essential for the initiation and amplification of antigen presentation during the immune response.This study investigates the reciprocal activating interaction between human peripheral blood natural killer (NK) cells and monocyte-derived immature dendritic cells (DC). The results show that NK cells, when activated by IL-2 or by mature DC, enhance DC maturation and interleukin (IL)-12 production. Conversely, immature DC, when exposed to maturation stimuli such as LPS, Mycobacterium tuberculosis, or IFN-α, significantly enhance NK cell cytotoxicity and CD69 expression. The interaction is cell contact-dependent, although the secretion of IFN-γ and TNF also contributes to DC maturation. The reciprocal activating interaction was restricted to NK cells, as other lymphocyte subsets did not express CD69 or mature upon contact with DC. These findings demonstrate a bidirectional cross talk between NK cells and DC, where NK cells activated by IL-2 or by mature DC induce DC maturation. The study also shows that IL-2-activated NK cells directly induce DC maturation and enhance their ability to stimulate allogeneic naive CD4+ T cells. The effects of NK cells on DC maturation were found to depend on cell-to-cell contact, although the secretion of IFN-γ and TNF also contributed to DC maturation. The study highlights the importance of NK cells in the immune response, as they not only act as effector cells of innate resistance but also regulate adaptive immunity. The findings suggest that NK cells play a crucial role in the activation and maturation of DC, which in turn enhances the immune response. The study also indicates that the interaction between NK cells and DC is regulated to prevent unnecessary activation of self-reactive or bystander cells. The results suggest that the cross talk between NK cells and DC is essential for the initiation and amplification of antigen presentation during the immune response.