UCSF

Key PointsEmerging data provide evidence that natural killer (NK) cells can contribute to immunological memory, an activity that has traditionally been associated with T cells and B cells. Three main types of NK cell memory exist, namely hapten-specific NK cell memory, virus-specific NK cell memory and cytokine-induced NK cell memory.Distinct receptor–ligand interactions and distinct cytokine milieus lead to the generation of antigen-specific memory NK cells. Cytokine-induced memory NK cells can be generated by exposure to inflammatory cytokines even in the absence of a defined antigen.The different types of memory NK cells differ in terms of their tissue localization patterns. For example, hapten-specific memory NK cells reside in the liver, influenza virus-specific memory NK cells reside in the liver and lung, and mouse cytomegalovirus (MCMV)-specific NK cells and cytokine-induced memory NK cells are systemically distributed.Most of our mechanistic knowledge of the signals that drive the generation of virus-specific memory NK cells originates from experiments using MCMV infection as a model system. These studies have identified LY49H as the MCMV-specific activating NK cell receptor and m157 as the cognate viral ligand recognized by LY49H.The basic concepts derived from studying NK cell memory might lead to novel strategies for refining vaccination protocols to improve treatments for infectious diseases.It is possible that NK cell memory activity could be exploited for cancer therapy. Lessons learned from the study of NK cell memory could help with the design of better expansion protocols for adoptive NK cell therapy, for the manufacturing of chimeric antigen receptor (CAR)-engineered NK cells and for improving NK cell-based therapies that rely on antibody-dependent cellular cytotoxicity (ADCC).