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 rnononuclear 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 mu g/ml). The cells were labeled with conjugated antibodies specific for CD4,CD8, CD28, CD45RO, and Fas, and were analyzed by FACS((R)). 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 (R-2 = 0.76, p < 0.000 1). Compared to other biomarkers (CD28(-), CD28(-)CD45RO(+), and Fas(+)) that have been associated with CD8(+) T-cell aging, the loss of the CD28(+) Fas(-) CW8(+)-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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.