Memory-like NK cell formation. (a) Antigen-dependent memory-like NK cells. During CMV infection, NK cell memory is generated. In mouse it occurs through the recognition of MCMV m157 protein by the activating Ly49H receptor, while in human the ligand involved has not been identified yet; nevertheless, HCMV infection is associated with the expansion of CD94/NKG2C+ NK cell population. Hapten-specific memory-like NK cells are generated in the liver of a mouse model of hapten-induced contact hypersensitivity (CHS). Among the hepatic NK cell populations, CD49a+/DX5− NK cells confer hapten-specific CHS memory-like responses, while the expression of CXCR6 is believed to have a role in their liver homing. (b) Antigen-independent long-lived cytokine-activated NK cells. They are generated after exposure to cytokines (IL-12, IL-15, and IL-18) and are characterized by prolonged longevity, CD25 expression, and intense IFN-γ production upon restimulation. (c) Hepatic localization of memory-like NK cells in CHS model. (1a) NK cells are activated in draining lymph nodes by antigen presenting cells, and newly generated memory-like NK cells move into the liver. Alternatively, (1b) antigenic recognition by NK cells directly occurs in the liver. (2) Second exposure to the hapten activates CD49a+/DX5− memory-like NK cells and (3) migration of CD49a−/DX5+ NK cells into organs where the hapten is present.