Natural killer cell memory in context

Immune memory has traditionally been considered a hallmark of vertebrate T and B lymphocytes. However, given the advantage in mounting quicker and more robust responses to recurrent infection, it is unsurprising that alternative strategies of memory are found in various immune cells throughout the evolutionary tree. In this context, a variety of NK cell memory subsets have recently been identified. Mouse models of cytomegalovirus infection have been instrumental in revealing the kinetics and molecular mechanisms of long-lived NK cell memory. Moreover, murine liver-resident memory NK cell subsets have been identified that potentially harbour antigen-specificity. Phenotypic counter-parts have recently been characterised in the human liver, adding to the mounting evidence suggesting that a spectrum of NK cell memory subsets exist in primates. These include cytomegalovirus-associated peripheral blood NK cell expansions that in humans have been shown to harbour epigenetic alterations that impact cellular phenotype and function. Here we discuss some general mechanisms of non-classical immune memory. We highlight themes of commonality that may yield clues to the molecular mechanisms of NK cell memory, whilst emphasising some outstanding questions.