Abstract
Natural killer (NK) cells are a unique lymphocyte lineage with remarkable agility in the rapid destruction of virus-infected cells. They are also the most poorly understood class of lymphocyte. A spectrum of activating and inhibitory receptors at the NK cell surface leads to an unusual and difficult-to-study mechanism of cellular recognition, as well as a very high capacity for diversity at the single-cell level. Here, we review the evidence for the role of NK cells in the earliest stage of human viral infection, and in its prevention. We argue that single-cell diversity is a logical evolutionary adaptation for their position in the immune response and contributes to their ability to kill virus-infected cells. Finally, we look to the future, where emerging single-cell technologies will enable a new generation of rigorous and clinically relevant studies on NK cells accounting for all of their unique and diverse characteristics.
Highlights
Specialty section: This article was submitted to Natural killer (NK) Cell Biology, a section of the journal Frontiers in Immunology
We review the evidence for the role of NK cells in the earliest stage of human viral infection, and in its prevention
In addition to several mutations known to exert their effects on NK cells in relative isolation, at least 46 primary immunodeficiencies are associated with NK cell defects. These subjects’ overarching and unifying feature is the unusual susceptibility to herpesviruses [54], especially HSV-1, EBV, VSV, and HPV. These findings suggest that NK cells play a non-redundant role in preventing the establishment of these infections
Summary
In comparison to their classic innate and adaptive counterparts, NK cells take an intermediate position in estimates of cellular lifetime (Figure 1). Human T cells have the longest estimated leukocyte half-lives, at 1–8 years for naive T cells and 1–12 months for memory T cells [9, 10]. It is important to note that only actively dividing cells incorporate deuterium, and these studies may not account for long-lived, non-dividing cells. They are based entirely in peripheral blood; cell kinetics in tissues may follow completely different patterns. With these caveats in mind, these data suggest that NK cells fall midway on the spectrum of cellular lifetime. These estimates may serve as a reasonable proxy for the amount of time they require to respond to viral infection
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