CD56^bright and CD56^dim NK-cell interactions. (A) NK-DC interactions in secondary lymphoid tissue (SLT). (1) Activated mature DCs (mDCs) enter SLT from periphery or (2) immature DCs (iDCs) receive pathogens within SLT. Each express and/or secrete a variety of cytokines (3) that are required for NK-cell maturation and survival (eg, DC IL-15) and NK cell proinflammatory cytokine production (eg, DC IL-12 in combination with DC IL-1, IL-15, IL-18). Activated CD56^bright NK cells in turn secrete TNF-α and GM-CSF that contribute to DC maturation, (4) and IFN-γ that contributes to DC activation and thus indirectly to antigen-specific T-cell priming (5). NK-cell IFN-γ also contributes directly to T-cell priming (6). NK cells can kill immature autologous DCs (7) via NKp30, which may assist in editing out hyporesponsive DCs or by limiting T-cell priming.^33,34  (B) Summary of NK-cell recognition. The functional consequences of NK-cell receptor recognition depend on the integration of both inhibition and activation signals received in response to engagement of target cell ligands.^58,59  Upper left: normal autologous tissues are not attacked because the predominant signal is recognition of self-MHC class Ia ligands by inhibitory KIRs (and other inhibitory receptors such as NKG2A/CD94 recognizing their ligands, not shown) in the absence of ligands for activating NK receptors. Upper right: Malignant autologous tumors such as acute myeloid leukemia (AML) have high-density surface expression of classical MHC class Ia and nonclassical MHC class I that that bind to KIR and NKG2A/CD94, respectively, and dominate over engagement of NK-cell activation receptors with their cognate ligands. Lower left: Normal allogeneic host tissue presumably lacks ligands that engage dominant activating NK receptors such as NKG2D and NCR, despite a mismatch of donor NK KIR with host MHC class Ia as well as donor NKG2A/CD94 and host HLA-E (not shown). Lower right: A mismatch of donor NK KIR and host MHC class Ia in the presence of ligand-engaged NKG2D, NCR, and other NK activation receptors⁶⁰  likely contributes the dominant NK response of target cell lysis.^48,61,62  Illustration by Debra T. Dartez.