Abstract
Abstract Natural killer (NK) cells play an important role in shaping the immune response by releasing proinflammatory cytokines and direct lysis of malignant or virus-infected cells. However, very little is known about the earliest phases of the human NK cell response after acute infection in vivo. Here we made use of the yellow fever virus (YFV) vaccine strain 17D as an in vivo model of an acute viral infection in humans. Vaccination with the live attenuated 17D yellow fever strain induces a measurable viral load and strong T cell activation. YFV vaccination activated NK cells in vivo with distinct kinetics for different functions. NK cell activation as measured by upregulation of Ki67 peaked at day 10, whereas increased degranulation and cytokine production by NK cells peaked at day 6, and coincided with a peak in type I interferons and viral load. Interestingly, within the CD56dim NK cell population, activation was strongest in the least differentiated subset, but was independent of NK cell education via killer cell Ig-like receptors (KIRs). In conclusion, vaccination with 17D allows a detailed longitudinal analysis of NK cell activation after an acute viral infection in humans, and reveals a hierarchy of activation among different NK cell subsets.
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