In HLH, an increased proportion of CD38^high/HLA-DR⁺ T cells produce cytokines (eg, TNF and IFN-γ) that drive the activation of innate immune cells, such as macrophages, natural killer cells, and dendritic cells. In early sepsis, there is limited to no evidence of CD8 T-cell activation, nor is there increased expression of CD38 or HLA-DR on T cells. The figure was created with BioRender.com.