A role for NK cells in the generation of antitumor CD8 T cell responses has been linked to their ability to increase inflammation via secreting IFN-c and promoting IL-12 production by DCs [71, 72] . Collectively, these studies and ours reveal a role for NK cells as mediators of an ''innate cytokine balance'' for the optimal generation of the immune response, whereby NK cells are required to produce cytokines to increase inflammation when it is intrinsically low (during tumor development) and to prevent excessive production of innate cytokines when it can be intrinsically high (in the context of pathogenic encounters). Of note is the apparent requirement, in both instances, for NK cells to engage in cognate receptor-mediated interactions to naturally develop immunoregulatory functions. For example, during the response to MCMV, the systemic activation of NK cells by IL-12 to produce IFN-c in a Ly49H À environment is not sufficient to promote their control of viral replication and their associated immunoregulatory functions. These cognate interactions could also enable NK cells to act as direct regulators of antiviral immunity, as already illustrated for the generation of antitumor CD8 T cell responses. During the response to MCMV, Ly49H expression by NK cells dramatically increases the efficiency of recognition and killing of infected cells. Ly49H may also enable NK cells to deliver IFNc in a proper place and time to help the priming of antiviral CD8 T cells in infected mice through a tripartite interaction with MCMV-infected m157-expressing DCs. The importance of these cognate interactions for the promotion of efficient NK cell functions may differ depending on the tissues and on the target cell types, as exemplified by the heightened requirement for Ly49H-dependent mechanisms for MCMV control in the lungs [73] .