Fig. 7: The role of IL-18 in the downregulation of Eomes in NK cells.
a, b Newborn mice were intraperitoneally infected with 200 PFU of MCMV or mock-infected 24–36 h after birth. a Expression of Eomes by NK cells lacking TGF-β receptor (Tgfbr2f/fNcr1iCre) and control NK cells is shown (Tgfbr2f/f) 21 days post-infection. b Expression of Eomes by NK cells is shown for IL-12R knockout mice (IL12R −/−), type I interferon knockout mice (Ifnar−/−) and NKG2D knockout mice (Klrk1−/−) 21 days post-infection. Representative histograms are shown. c, d Splenic NK cells were isolated from naïve, 20 days old mice and cultured in IL-15 for 5 days. Cells were then cultured in the presence of IL-12 and IL-18 for 2 days. Quantification of KLRG1 and Eomes expression by NK cells is shown (n = 1 0 h, n = 5 24 h & 48 h; N = 2, One-way ANOVA test). Mean values ± SD are shown. e On day 21 post-infection the concentration of IL-18 was determined in the spleen (n = 4 mice per group, Mann–Whitney two-tailed test). Mean values ± SD are shown. f On postnatal days (PND) 10 and 60 the expression of IL-18R was analyzed on splenic NK cells. Representative histograms (left) and quantification (right) of IL-18R expression on NK cells are shown (n = 6 10 PND, n = 5 60 PND, Mann–Whitney two-tailed test). Mean values ± SD are shown. At indicated time points post-infection fold changes of bone marrow cellularity (g), NK cell precursors (h), and immature (i) and mature (j) NK cells were determined (n = 5 DPI5 & DPI12, n = 4 DPI22 & DPI40, n = 3 DPI80, Two-tailed Student’s t test). Mean values ± SD are shown. k On day 21 post-infection, C56BL/6 mice were euthanized, and bone marrow cells were transferred into Rag2-/-γc-/- mice. Seven days after adoptive transfer the number of splenic NK cells was determined in Rag2-/-γc-/- mice (n = 5 mice per group, Mann–Whitney two-tailed test). Mean values ± SD are shown. Statistically significant differences are indicated (P values). Source data are provided as a Source Data file.
