Figure 4|. Recombinant interleukin-21 (rlL-21) activates CD56^dimCD16^bright natural killer (NK) cells in vitro, enhancing their type 1 polarization and cytotoxicity.

(a) Phenotypic NK cell changes after 5-day in vitro stimulation with rlL-21. n = 4–11 healthy volunteers (HVs). Mann-Whitney test, (b) Phenotypic modifications after 5-day rlL-21 stimulation ± IL-21 receptor (IL-21 R) antagonist (IL-21 R-Fc). n = 4 HVs. Mann-Whitney test, (c) CD56^dimCD16^bright NK cell degranulation and cytokine production after 5-day rlL-21 stimulation, n = 12 HVs. Boolean gates were created for CD107a, interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10). Polyfunctional data were analyzed using the Simplified Presentation of Incredibly Complex Evaluations (SPICE) software. The pie charts display the mean frequencies of degranulating and/or cytokine-secreting CD56^dimCD16^bright NK cells for each possible combination of CD107a/IFN-γ/TNF-α/IL-10. Pie segments are color coded to represent monofunctionality to polyfunctionaiity. The arcs illustrate the analyte(s) produced by the pie segment underneath. Mann-Whitney tests were used to compare each pie segment between the 2 groups. Significance symbols were displayed on the pie segment with increased proportion. *P < 0.05, ***P < 0.001. CXCR3, CXC chemokine receptor 3; MFI, mean fluorescence intensity; NKG2A, natural killer group 2A; NKG2D, natural killer group 2D.