Early activation defects in T lymphocytes from aged mice

Abstract

Aging affects both calcium signals and protein kinase cascades in mouse T lymphocytes. The decline in calcium signal development largely represents differences between naive and memory T cells: the latter are resistant to increases in calcium concentration, and are more common in aged mice. Aging leads to declines in phosphorylation of a wide range of substrates in T cells stimulated by either anti-CD 3 antibodies or by substances, such as phorbol myristate acetate (PMA) or ionomycin, that act at intracellular sites, but some phosphoproteins respond only in old T cells, and others respond regardless of age, Tyrosine phosphorylation of die CD3Ζ chain declines with age, both in resting T cells and after activation. but the proportion of Zap-70 that is bound to CD3C increases in T cells from old mice, Zap-70 function and phosphorylation of CD3Ζ-associated Zap-70 change only slightly after stimulation of T cells by anti-CD3 and aiHi-CD4, and are at similar levels in activated old and young T cells. Nonetheless, induction of Raf- l, MEK, and ERK kinase activity declines with age in CD4T cells. The effect of aging on T-cell activation is not simply an overall decline in signal intensity, but a set of qualitative changes that differ among subsets and depend at least partly on the nature of the stimulus.