Abstract
NK cells are cytotoxic lymphocytes that provide systemic defense against pathogens and malignancy. Although historically considered cells of the innate immune system, NK cells are now known to be capable of memory or memory-like immune responses in certain settings. Memory NK responses were initially reported over a decade ago in studies involving mouse models of cytomegalovirus infection and delayed-type hypersensitivity reactions to chemical haptens and viral antigens. Since then, a growing body of literature suggests that memory or memory-like NK cell responses may occur in a broader range of immunological settings, including in response to various viral and bacterial infections, and some immunization protocols. Memory-like NK cell responses have also now been reported in humans and non-human primates. Here, we summarize recent studies demonstrating memory or memory-like responses by NK cells in settings of infection and immunization against infectious agents.
Highlights
Natural killer (NK) cells are cytotoxic lymphocytes specialized for immunological defense against malignant cells and intracellular pathogens
Expansion of NKG2C+ NK cells in these settings may reflect antibody-driven proliferation of the FcεRIγ− population that is abundant in human cytomegalovirus (HCMV)-seropositive individuals, consistent with studies showing that FcεRIγ− NK cells expand in vitro following exposure to target cells infected with HCMV, herpes simplex virus (HSV)-1, or influenza, but only when virus-specific antibodies are present (Lee et al, 2015)
Whether and how NKG2 receptors contribute to antigen-specific NK responses to human immunodeficiency virus (HIV) antigens in macaques; why NKG2C+ and NKG2A+ populations are associated with memory-like responses to HCMV and EpsteinBarr virus (EBV) in humans, respectively; and whether the KIR3DS1+ and KIR3DL1+ NK cells that expand during HIV infection in humans become memory cells are important and open questions in the field
Summary
Natural killer (NK) cells are cytotoxic lymphocytes specialized for immunological defense against malignant cells and intracellular pathogens. Analogous to the MCMV-specific memory responses demonstrated in mice, memory-like NK cell populations have been described in humans with a history of human cytomegalovirus (HCMV) infection.
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