Anti-IL-15 administration results in near-complete NK cell depletion in AGMs. (a) Schematic representation of the anti-IL-15 treatment schedule used in this study. Five chronically infected AGMs received 20 mg per kg body weight (mg/kg) of anti-IL-15 monoclonal antibody (Ab) on day 0 and 10 mg/kg on day 14. Red arrows show the days when anti-IL-15 monoclonal antibody was administered. The blue arrow indicates the day of necropsy (Nx). (b) Dot plots showing NK cells (CD3−NKG2A+) in peripheral blood from one representative AGM before and after anti-IL-15 administration. The numbers represent the percentages of NK cells among CD45+CD20− cells. (c) Follow-up of NK cells in blood and LN. Blood was analyzed for five monkeys. LNs were available for four and five monkeys at day 21 and day 42 post-treatment, respectively. For blood, gray and purple lines represent the trajectories for individual animals and the median values for all monkeys, respectively. For statistical analyses, mean values for the three preinfection time points were used for c–f. (d) Follow-up of CD4+ T cells and subpopulations of CD4+ T cells in blood during anti-IL-15 treatment. TN, naive T cells; TM, central memory T cells; TE, effector memory T cells. (e) Follow-up of CD8+ T cells and subpopulations of CD8+ T cells in blood during anti-IL-15 treatment. (f) CD4+ T cells and CD8+ T cells positive for Ki-67 in blood. In c–f, black arrows indicate the days when anti-IL-15 monoclonal antibody was administered. (g) CD4+ T cells in LN. (h) CD8+ T cells in LN. In g and h, parent cells are CD4+CD3+ and CD8+CD3+, respectively. (i) CD4+ T cell subpopulations in LN. (j) CD8+ T cell subpopulations in LN. Median values and interquartile range are shown for g–j. Each dot represents the value for an individual animal. Nonparametric Mann–Whitney U-tests were applied. *P < 0.05, **P < 0.005.