CD8 T-cell immune phenotype of successful aging

The nonagenarian population by definition represents individuals who have demonstrated success in aging. We determined the status of CD8+ T-cell senescence in nonagenarians by analyzing the expression of CD28 and Fas (CD95), and analyzing activation and activation-induced cell death (AICD). Peripheral blood mononuclear cells (PBMCs) were isolated from three groups of subjects: adults (20–64-year-old), older adults (65–89-year-old), and nonagenarians (≥90-year-old). PBMCs were stimulated with phytohemagglutinin (PHA) (10 μg/ml). The cells were labeled with conjugated antibodies specific for CD4, CD8, CD28, CD45RO, and Fas, and were analyzed by FACS®. There was a strong negative correlation of the percentage of CD28+Fas− CD8+ T-cells with the age of each individual prior to stimulation in vitro (R2 = 0.76, p < 0.0001). Compared to other biomarkers (CD28−, CD28−CD45RO+, and Fas+) that have been associated with CD8+ T-cell aging, the loss of the CD28+Fas− CD8+ T-cell population exhibited the strongest correlation with the individual's chronologic age. After stimulation with PHA, there was a decrease in the percentage of CD8+ T-cells from individual ≥65-year-old that expresses both CD28+ and Fas+ at day 3. Surprisingly, the AICD response of CD8+ T-cells at day 7 in the nonagenarians was higher than that in the other two groups. These results suggest that successful aging does not prevent development of the senescent phenotype of unstimulated CD8+ T cells, but is associated with preservation of CD8 T cell functions including activation and AICD. Increased AICD may result in enhanced rejuvenation capacity of T cells and limit the impact of aging on T cell function in nonagenarians.