Chronic stimulation of an aged immune system is thought to result in CD8 + CD28− TEMRA cells, which are associated with decreased responsiveness.78 In contrast, the absence of CD28 on CD4 + TEMRA cells is usually transient and activation-induced, and the presence of CD4 + CD28− cells have been associated with vascular inflammation and stroke.80–82 Thus, immune-senescence in CD8 + T cells may be sequelae of chronic inflammation resulting in biological frailty, and dysfunction in the CD4 + subset may be an indicator for actively declining health. The gene discussed is CD28; the disease is Stroke.