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. © 2005 Elsevier Ireland Ltd. All rights reserved.
Publication Source (Journal or Book title)
Mechanisms of Ageing and Development
Hsu, H., Scott, D., Zhang, P., Zhou, J., Yang, P., Wu, Q., Schroeder, H., Gerald, L., Ravussin, E., Jazwinski, S., Mountz, J., Batzer, M., Black, M., Broussard, E., Byerley, L., Callinan, P., Cherry, K., Chiu, Y., Cooper, A., DeLany, J., Deutsch, W., Fontham, E., Frisard, M., Geiselman, P., Greco, V., Hawley, K., Herke, S., Jazwinski, S., Kendzor, D., Kim, S., Kimball, B., Li, L., Lopez, K., & Ravussin, E. (2006). CD8 T-cell immune phenotype of successful aging. Mechanisms of Ageing and Development, 127 (3), 231-239. https://doi.org/10.1016/j.mad.2005.10.001