IL-15 treatment preferentially targets memory T cells and induces their proliferation and the expression of multiple activation markers. (A) Representative example of Ki-67, CD25 (only on CD4⁺ cells, top part of the figure), and CD38 (only on CD8⁺ cells, bottom part of the figure) expression in a RM receiving 50 μg/kg/d IL-15. Bulk CD4⁺ and CD8⁺ T cells were identified as in Figure 2C. Data for different subsets of T cells (T_N, defined as CCR7⁺CD95⁻; central memory, T_CM, as CCR7⁺CD95⁺; effector memory, T_EM, as CCR7^–CD95⁺) are shown for day −7 (pretreatment), 8, 15, and 48 after the first injection. Numbers in the plots indicate the percentage of cells belonging to each quadrant. (B) Percentage of T_CM and T_EM CD4⁺ and CD8⁺ T cells expressing Ki-67, CD25, and CD38 and mean fluorescence intensity (MFI) values of IL-15 receptor components (CD122 and CD132) in the same subsets during IL-15 therapy. Values for naive T cells are not shown, as little changes could be observed for these markers compared with pretreatment. Horizontal black, bold bars indicate the median. Values from single animals were overlayed and were depicted as blue (sham) or red (IL-15–treated) dots. *P < .05 for Wilcoxon rank test versus day −7.