Memory of Infections: An Emerging Role for Natural Killer Cells

Many previous reports on Natural Killer (NK) cells highlighted their ability to form the proverbial first line of defense against a variety of viral infections and malignancies. NK cells have been considered a part of innate immunity, characterized by invariant, germ-line encoded receptors for the recognition of pathogens and infected cells. In contrast, somatic rearrangement of receptor genes, the clonal expansion of antigen-specific cells, and the ability to mount a more potent memory response upon secondary challenge are traditionally considered hallmarks of T and B cells belonging to the adaptive immune system. More recently, exciting new data are challenging this conventional view [1]. A growing body of evidence indicates that under certain experimental conditions, NK cells share some of the features of adaptive immune cells. For instance, in mice infected with murine cytomegalovirus (MCMV), an NK cell subset expands in an antigen-dependent manner reminiscent of the clonal expansion of adaptive immune cells [2]. This NK cell expansion is associated with long-lasting functional changes similar to features of memory T cell populations. Resemblances between NK and T cells are not only limited to their response kinetics and certain functions, but also comprise characteristics of homeostatic proliferation, development, and differentiation [3]. Currently, a clear consensus on how the term “memory” is defined in NK cell biology is lacking. Throughout this article we will refer to memory NK cells, if these NK cells respond more potently to a second challenge with the same antigen they had initially encountered (Figure 1). The term “memory-like” NK cells will be used when long-lasting functional alterations are induced, e.g. by cytokines without clear evidence of antigen involvement (Figure 1). Figure 1 Memory and memory-like NK cells in mice and humans.