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(1o)CD25(+)CD28(1o) 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. (C) 2004 Elsevier Inc. All rights reserved.