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 (>or=90-year-old). PBMCs were stimulated with phytohemagglutinin (PHA) (10 microg/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<0.0001). 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 >or=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.
Hsu
Hui-Chen
HC
The University of Alabama at Birmingham, Department of Medicine, Division of Clinical Immunology Rheumatology, 701 South 19th Street, LHRB 473, Birmingham, AL 35294, USA.
Scott
Donald K
DK
Zhang
Pili
P
Zhou
Juling
J
Yang
PingAr
P
Wu
Qi
Q
Schroeder
Harry W
HW
Gerald
Lynn B
LB
Ravussin
Eric
E
Jazwinski
S Michal
SM
Mountz
John D
JD
D000328:Adult; D000375:Aging / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D018106:CD28 Antigens / Q000096:biosynthesis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D019014:fas Receptor / Q000096:biosynthesis / Q000276:immunology*
D015415:Biomarkers; D018106:CD28 Antigens; D010835:Phytohemagglutinins; D019014:fas Receptor