Decreased proliferative capability of CD4(+) cells of elderly people is associated with faster loss of activation-related antigens and accumulation of regulatory T cells

Decreased proliferation of CD4(+) lymphocytes of elderly people is at least in part due to lowered proportion of cells that are capable of dividing and producing viable progeny (effective precursors). We show that age-dependent reduction in effective precursor numbers depends on the one hand, extensive, activation-dependent apoptosis occurring from the very onset of stimulation and, on the other, the accumulation of non-dividing, regulatory (suppressor) CD4(lo)CD25(+)CD28(lo) T cells. In addition, analysis of changes in surface expression of activation-related antigens, including CD25, CD69, and PCNA in consecutive generations of dividing CD4(+) cells traced by carboxyfluorescein diacetate succinimidyl ester staining showed variable patterns of these changes that may relate to various aspect of impaired division of these cells in elderly.