Antigen-receptor stimulation drives purifying selection against pathogenic mitochondrial DNA variants that dysregulate lymphocyte responses

Metabolic transcriptomic signatures of CD8+ T cells during timecourse activation were profiled in CD8 T cells isolated from 4 WT and 4 C5024T mice. Mice were age (2-month-old) and sex matched. Briefly, for each mouse, freshly purified (negative selection) splenic naïve CD8+ T cells were seeded at a density of 200,000 cells/well and activated using a 1:1 (bead:cell) ratio with Dynabeads Mouse T-Activator CD3/CD28 for 6 and 96 hr at 37oC (5% CO2) . 200,000 ex vivo purify ed naïve CD8+ T cells were collected for baseline (0 hr) measurement. 4wt and 4 C5024T mice,from each mice, sub-divided into three groups: naive CD8 T cell, CD8 T cell post_6h activation, CD8 T cell_post 96h activation.