Analysis of CD8 T cells in aged mice

Aging is associated with systemic chronic inflammation (inflammaging) that leads to impaired physiological functions and vulnerability to several diseases. However, underlying alterations in aged immune system resulting in gradual loss of immune fitness remain unclear. Using a combination of bulk and single-cell RNA sequencing, we characterized the age-associated alterations in CD8 T cells. We defined organ-specific and common changes in immune cell populations and identified a distinct subpopulation of granzyme K (GZMK)-expressing clonal CD8+ T cells that accumulate with age in multiple tissues. These cells have a distinct epigenetic signature, express markers of exhaustion but, paradoxically, show an increased capacity to produce mediators of inflammation that increase secretion of inflammatory cytokines from non-immune cells. Our findings suggest that accumulation of GZMK+ CD8+ T cells is a conserved hallmark of inflammaging. Overall design: Viable CD3e+CD8a+CD44-PD1-, CD3e+CD8a+CD44+PD1- and CD3e+CD8a+PD1+ cells were sorted from spleen of 4 57BL/6J 18 months old female mice and total RNA was immediately isolated.