Monkey CD16+ NK Cells

Distinct Trafficking Kinetics of Natural Killer Cell Subsets in Non-Human Primates

To characterize the in vivo tissue distribution and trafficking dynamics of Natural Killer (NK) cells, Mortlock et al. utilized serial intravascular staining (SIVS) in rhesus macaques. Five healthy animals received anti-CD45 SIVS antibody infusions at specific intervals prior to tissue harvest (Fig. 1A). By quantifying SIVS labeling in peripheral blood mononuclear cells (PBMCs), the vascular residence time of CD56⁺, DN (double-negative), and CD16⁺ NK cell subsets was determined (Fig. 1B).

Analysis revealed distinct subset-specific behaviors. In animals receiving a 48-hour SIVS time-course, the majority of CD56⁺ NK cells in the peripheral blood were negative for the 6-hour antibody, indicating recent emigration from tissues within the last 6 hours (Fig. 1C). Conversely, most CD16⁺ NK cells remained positive for all SIVS infusions, demonstrating sustained vascular residence. DN NK cells exhibited intermediate kinetics, with 25%-50% retained in the vasculature throughout the experiment. Short-term (6-hour) SIVS profiles confirmed this hierarchy: CD16⁺ NK cells had the longest blood retention, followed by DN, while CD56⁺ NK cells showed the highest rate of tissue-to-blood trafficking.

Quantification of "Continuously Circulating" (CC) cells showed that CD56⁺ NK cells consistently had the lowest proportion of CC cells, while CD16⁺ and DN subsets had significantly higher rates (Figs. 1D, E). These data indicate that while the dominant CD16⁺ and DN NK cell populations (constituting >95% of circulating NK cells) remain in continuous vascular circulation, the minor CD56⁺ subset exhibits frequent trafficking between blood and tissues.