TY - JOUR
T1 - Age-dependent changes in the susceptibility to apoptosis of peripheral blood CD4+ and CD8+ T lymphocytes with virgin or memory phenotype
AU - Salvioli, Stefano
AU - Capri, Miriam
AU - Scarcella, Elena
AU - Mangherini, Sandro
AU - Faranca, Irma
AU - Volterra, Vittorio
AU - De Ronchi, Diana
AU - Marini, Marina
AU - Bonafè, Massimiliano
AU - Franceschi, Claudio
AU - Monti, Daniela
PY - 2003/4/1
Y1 - 2003/4/1
N2 - Susceptibility to apoptosis changes with age and most of the available data on lymphocytes refer to mitogen stimulated cells. We studied this susceptibility in quiescent, purified CD4+ or CD8+ T cells from a group of Italian old people compared with a group of young people. We found that an apoptotic agent such as 2-deoxy-D-ribose (dRib), which acts via glutathione depletion and oxidative stress, was more effective in CD4+ T cells from young donors, while no difference was found in CD8+ T cells. On the contrary, another agent such as TNF-α, which acts via receptor engagement, was more effective in CD8+ T cells from old subjects, and no difference was found in CD4+ T cells. When marker of activation-memory were investigated, no difference between young and old subjects was found when dRib was used. Differently, when TNF-α was used, memory and activated CD4+ T cells from old donors were less sensitive than younger counterparts, while memory CD8+ T cells from old donors were more sensitive than younger counterparts. This suggests that age-related changes in susceptibility to apoptosis of resting T cells largely depend on the type of the apoptotic stimulus which is used as well as on the memory phenotype of the cells. These results may also account, at least in part, for the deep remodelling of T cell repertoire that occurs during ageing.
AB - Susceptibility to apoptosis changes with age and most of the available data on lymphocytes refer to mitogen stimulated cells. We studied this susceptibility in quiescent, purified CD4+ or CD8+ T cells from a group of Italian old people compared with a group of young people. We found that an apoptotic agent such as 2-deoxy-D-ribose (dRib), which acts via glutathione depletion and oxidative stress, was more effective in CD4+ T cells from young donors, while no difference was found in CD8+ T cells. On the contrary, another agent such as TNF-α, which acts via receptor engagement, was more effective in CD8+ T cells from old subjects, and no difference was found in CD4+ T cells. When marker of activation-memory were investigated, no difference between young and old subjects was found when dRib was used. Differently, when TNF-α was used, memory and activated CD4+ T cells from old donors were less sensitive than younger counterparts, while memory CD8+ T cells from old donors were more sensitive than younger counterparts. This suggests that age-related changes in susceptibility to apoptosis of resting T cells largely depend on the type of the apoptotic stimulus which is used as well as on the memory phenotype of the cells. These results may also account, at least in part, for the deep remodelling of T cell repertoire that occurs during ageing.
KW - 2-Deoxy-D-ribose
KW - Aging
KW - Apoptosis
KW - Immunosenescence
KW - Memory T lymphocytes
KW - TNF-α
KW - Virgin T lymphocytes
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U2 - 10.1016/S0047-6374(03)00016-2
DO - 10.1016/S0047-6374(03)00016-2
M3 - Article
C2 - 12714247
AN - SCOPUS:0037396495
VL - 124
SP - 409
EP - 418
JO - Mechanisms of Ageing and Development
JF - Mechanisms of Ageing and Development
SN - 0047-6374
IS - 4
ER -