CD38^high/HLA-DR⁺CD8⁺T cells in patients with HLH are proliferative and display evidence of recent and persistent activation. (A-E) Representative flow cytometry plots from patients with HLH and composite data comparing controls and patients with sepsis or HLH, showing the indicated markers of activation, proliferation, and persistent stimulation (top of each panel). For controls and patients with sepsis, frequency shown is derived from gating on the top 10% of CD38-expressing CD8⁺ T cells, as CD38⁺/DR⁺ T cells are largely absent in these samples (bottom of each panel). Data are representative of 18 to 27 pediatric controls, 5 to 18 patients with sepsis, and 11 to 36 patients with HLH. Error bars represent median with 95% CI. Differences between indicated groups were calculated using the unpaired Student t test. **P < .01; ***P < .001; ****P < .0001.