Abstract
Mounting experimental evidence hints to an import role for natural killer (NK) cells in adaptive immune responses to pathogens. NK cells with adaptive features are heterogeneous and belong to different subsets according to their phenotype as well as the nature of their adaptive recall reactions. Three types of adaptive NK cell responses have been described: (i) NK cells with long-lived memory of multiple different haptens and viral antigens were described in murine liver tissue with a possible human counterpart; (ii) infection of human and mouse cytomegalovirus is associated with an expansion of NKG2C+ and Ly49H+ NK cells, respectively, that selectively recognize CMV-encoded peptides thereby facilitating recall responses; (iii) cytokine-stimulated NK cells respond to different stimuli with enhanced production of IFN-γ after re-stimulation. These exciting findings not only support the idea of NK cells with adaptive features, but define a novel field of harnessing memory NK cell subsets for therapeutic strategies.
Highlights
Immunological memory is a hallmark of adaptive immunity with leukocytes recognizing a previously encountered antigen and facilitating a specific and rapid immune response
The traditional view included that innate immune cells rapidly respond to pathogens, are critical in controlling viral infections and participate in tumor immunosurveillance in a non-specific fashion, but are unable to differentiate into memory cells (Lanier, 2005, 2007)
In this review we summarize and categorize the current understanding of natural killer (NK) cells with adaptive features
Summary
Immunological memory is a hallmark of adaptive immunity with leukocytes recognizing a previously encountered antigen and facilitating a specific and rapid immune response. NK cells isolated from human peripheral mononuclear cells are T-bethi and Eomeslow in spite of hepatic NK cells expressing low levels of T-bet (Knox et al, 2014; Stegmann et al, 2016) Their function could not be directly linked to memory until a recent study demonstrated antigen-specific recall responses of NK cells in a humanized mouse model. According to a recently published study human blood-derived NK cells exhibit antigen-specific cytotoxicity upon vaccination against or infection with hepatitis B (Wijaya et al, 2020) It is unclear whether (i) there is a well-defined subset of NK cells that is distinct in function and phenotype and (ii) this NK cell subset originates in the liver and appears in the blood stream en route to effector sites, as proposed previously (Paust et al, 2010b).
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