Fig. 3.

CD8+ T cells from adults with trisomy 21 show increased expression of inhibitory receptors and senescence markers. Fresh PBMCs from individuals with and without DS were stimulated ex vivo with PMA/Ionomycin before flow cytometry analysis. (A) (Top) Representative histograms showing the expression levels (MFI) of PD-1 and TIGIT on total CD8+ T cells from individuals with T21 (blue) and typical controls (D21, black) compared to FMO on CD8+ T cells (white). (Bottom) Display frequencies of PD-1 and TIGIT positive events among CD8+ T cells (n = 19 D21; n = 12 T21). (B) (Top) Pie charts illustrating the mean percentage of inhibitory receptor coexpression on total CD8+ T cells from people with and without T21 (n = 19 D21; n = 12 T21). Pie chart colors correspond to the number of inhibitory receptors expressed on a cell. Arcs around the pie represent which inhibitory receptor(s) are expressed. (Bottom) Coexpression of PD-1, TIGIT, and BTLA among CD8+ T cells. (C) Representative (Top) histograms and (Bottom) frequencies of CD57 and KLRG1 expression among CD8+ T cells (n = 19 D21; n = 12 T21). (D) Representative (Top) flow cytometric data and (Bottom) frequencies for coexpression of the senescence markers KLRG1 and CD57 among CD8+ T cells. (E) Heatmap showing the frequencies of PD-1, TIGIT, KLRG1, CD57, and PD1/KLRG1/CD57 positive events within the different subsets of CD8+ T cells, as defined in SI Appendix, Fig. S2C, in individuals with and without T21. (F) (Left) Pie charts as in B showing the coexpression pattern of the effector molecule IFN-γ and the indicated inhibitory receptors and senescence markers on the CD8+ T cell population (n = 19 D21; n = 12 T21). (Right) Coexpression of IFN-γ with PD-1, KLRG1, and CD57 among CD8+ T cells. Data in A–F are shown as mean ± SEM with significance determined by unpaired t test. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.