CD8A and Mitochondrial encephalopathy: Notably, these findings mirror our recent observations of purifying selection against pathogenic mtDNA mutations in CD8+ TEM cells in individuals with congenital mitochondriopathies, including patients with Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episode (MELAS) (11, 12) and Pearson Syndrome (13, 14), which is driven by the distinct demand for OXPHOS capacity during T cell proliferation and differentiation after activation (22, 23), refining decades of observation of purifying selection of pathogenic alleles in peripheral blood (15).