DS mice bearing the P14 transgene succumb to hyperinflammation but develop breakthrough GP33^TET-negative CD8 T-cell activation. (A-C) Splenomegaly, thrombocytopenia, and systemic IFN-γ in DS^KO, DS^KO-P14, and control mice. (D) Representative flow cytometry plots of splenic CD8 T cells. (E) Proportion of splenic CD8 T cells that bind GP33^TET. (F) Proportion of the activated (IL-18R1+) CD8 T-cell pool occupied by GP33^TET-negative cells. Graphs show combined data from 3+ experiments, each point represents an individual mouse. P values determined by two-way ANOVA (A) or one-way ANOVA with Tukey multiple comparisons test of pairwise comparisons against WT-P14 group.⁶²