Proliferation and apoptosis of human CD8(+)CD28(+) and CD8(+)CD28(-) lymphocytes during aging

It is commonly believed that the age-related decrease in the ratio CD28(+)/CD28(-) among CD8(+) T cells reflects replicative senescence of the lymphocytes. To verify this claim we measured the proliferation of CD8(+)CD28(+) and CD8(+)CD28(-) subsets by flow cytometry after PHA treatment of mononuclear lymphocytes from donors of different age, including centenarians. The fraction of CD28(+) cells decreases from ca. 80 to 40% (young to centenarians, respectively) with increasing age of the donors. Stimulation by PHA results in an increase in the ratio of CD28(+) relative to CD28(-) in all age groups. We found that not only CD8(+)CD28(+) but also CD8(+)CD28(-) cells were capable of proliferation. Moreover, the fraction of proliferation-competent CD28(-) cells was higher in the older donors compared with the younger ones. While PHA treatment led to apoptosis (as measured by DNA content and caspase-3 activation) of more than 20% of all lymphocytes, in the CD8(+) subset only ca. 10% died, irrespective of their CD28 status. Altogether, we showed over-representation of proliferating CD8(+)CD28(-) cells in aged people, which might not be particularly prone to undergo apoptosis.