Increased apoptosis of CD45RO- T cells with aging.
Increasing susceptibility to infectious and autoimmune phenomena have long been recognized to accompany advancing age in otherwise healthy individuals. Recently animal models of aging have suggested that age-associated immune dysfunction may correlate with defects in T cell apoptosis. We have examined activation-induced apoptosis defects in human peripheral T cells from young individuals (mean age = 31 +/- 3 years old) compared to aged individuals (mean age = 67 +/- 8 years old). Following in vitro activation of T cells with PHA and IL-2, apoptosis was measured in T cell subsets using 7-amino actinomycin D (7-AAD) staining and analysis via three colour flow cytometry. There was no significant difference in apoptosis of the total CD3+ T cell population at early and late time points. Interestingly, increased apoptosis in the CD3+ CD45RO- T cell population of older adults was observed by culture day 6. While the total number of CD3+ CD45RO- cells was not different between young (< 33 years) and old (> 65 years) individuals, 32% of these cells did not undergo apoptosis in younger individuals while only 10% of these cells avoided this fate in older individuals. These results suggest that accumulation of CD45RO+ T cells may occur in aged subjects due in part to preferential elimination of CD45RO- cells with activation. Furthermore, as new or continued immune response requires differentiation of CD45RO+ T cells to CD45RO+ T cells after activation, increased apoptosis instead of survival in aged individuals could lead to observed T cell immune deficiency.
Herndon
F J
FJ
Department of Medicine, University of Alabama at Birmingham 35294-0007, USA.
Hsu
H C
HC
Mountz
J D
JD
D000328:Adult; D000368:Aged; D000375:Aging; D017209:Apoptosis; D017252:CD3 Complex / Q000276:immunology*; D003609:Dactinomycin / Q000031:analogs & derivatives / Q000737:chemistry; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D017252:CD3 Complex; D005456:Fluorescent Dyes; D003609:Dactinomycin; C025942:7-aminoactinomycin D; D017493:Leukocyte Common Antigens