Figure 1.

STAT5-activating cytokines confer DEX resistance in CD8 T cells. (A) Levels of HLH-associated plasma proteins in plasma from control patients versus patients with HLH. (B) Viability relative to vehicle control of murine CD8 T cells treated with increasing concentrations of DEX or etoposide in the absence or presence of 10 ng/mL of the indicated cytokine for 24 hours in technical triplicate. (C) Fold change in the MFI of pSTAT5 in murine CD8 T cells stimulated with 100 ng/mL of the indicated cytokine for the indicated period of time in technical triplicate. Statistical significance is indicated for the difference between the basal condition and the peak pSTAT5 value for each cytokine. (D) Fold change and the representative histograms of pSTAT5 in murine CD8 T cells in the basal condition or after 1 hour of pretreatment with the indicated concentration of RUX followed by a 15-minute stimulation with 100 ng/mL of IL-2 in technical triplicate. Statistical significance is relative to the vehicle-treated IL-2-stimulated condition. (E) Viability relative to vehicle control of murine CD8 T cells treated with increasing concentrations of DEX in the presence of 10 ng/mL of IL-2 and the indicated concentration of RUX for 24 hours in technical triplicate. (F) Heatmap of Bliss independence scores calculated as the average of technical triplicates of cell viability in murine CD8 T cells treated with the indicated concentrations of DEX and RUX in the presence of 10 ng/mL of IL-2 for 24 hours. Positive values, indicated in red, are indicative of a synergistic interaction. Statistical significance was assessed using 2-sample Student t tests (A and C) or 1-way ANOVA with Tukey’s method for multiple comparisons adjustment (D). All data are representative of 3 independent experiments. ****P < .0001; ***P < .001; **P < .01; *P < .05. N.S., not significant.