Activated CD8⁺T cells in patients with HLH are predominantly effector memory T cells with Tc1 and cytotoxic differentiation. Representative flow cytometry plots from patients with HLH and composite data comparing controls and patients with sepsis or HLH, showing (A) frequency effector T-cell differentiation (CD45RA⁻ CCR7⁻) among CD38^high/HLA-DR⁺ CD8⁺ T cells. As CD38⁺/DR⁺ T cells are largely absent from healthy controls and patients with sepsis, frequency shown is derived from gating on the top 10% of CD38-expressing CD8⁺ T cells. (B-C) Expression of CD28 or granzyme B in CD38^high/HLA-DR⁺ CD8⁺ T cells is shown as in panel A. (D) Representative FACS plots and composite data showing CXCR3 expression in CD8⁺ CD38^high T cells of controls (top 10% of CD38 expressors) and patients with HLH. (E-F) Representative flow cytometry plots and composite data showing IFN-γ and TNF-α production among CD8⁺CD38^high cells in indicated populations after phorbol myristate acetate/ionomycin stimulation. Data are representative of 12 to 27 pediatric controls, 5 to 16 patients with sepsis, and 13 to 37 patients with HLH. Error bars represent median with 95% CI. Differences between indicated groups were calculated using the unpaired Student t test. *P < .05; **P < .01; ***P < .001; ****P < .0001.