ALPS “DNT-like” CD4⁺and CD8⁺ T cells show enhanced mitotic activity and mTOR signaling. CD4⁺ and CD8⁺ T cells of ALPS patients were gated for naive (CD45RA⁺/CD57⁻), TEMRA (CD57⁺/CD28⁻/CD27⁻), and “DNT-like” (CD57⁺/CD28⁺/CD27⁺) cells and analyzed for their Ki67 expression (A) or phosphorylation status after stimulation with anti-CD3/CD28 mAbs (B). Plots show representative data from 1 of 3 independent experiments with similar results. Y-axis in the histograms is normalized to mode. (C) PBMC from patients with ALPS before and under rapamycin therapy were stained with anti-CD3, anti-CD4, anti-CD8, anti-CD28, anti-CD57, and anti-Ki67 mAbs. Cells are gated for CD3⁺/CD4⁺ and CD3⁺/CD4⁺/CD57⁺ (left) or CD3⁺/CD8⁺ and CD3⁺/CD8⁺/CD57⁺/CD28⁻ (right). Representative plots show data of a patient with ALPS before and during rapamycin therapy; graphs present frequencies of 3 patients.