Differential regulation of actin polymerization following activation of resting T lymphocytes from young and aged...

Actin polymerization accompanies receptor-mediated responses and is correlated with motility-related events. In T lymphocytes, there is a lateral redistribution of surface receptors into caps and aggregation of actin-myosin in cytoplasmic subcaps, and these are impaired in T cells from aged individuals. This study documents marked changes in age-related cytoskeletal actin filament function which may account for the reduced motility. Basal levels of filamentous actin (F-actin) are significantly higher in purified G(o) T cells from aged C57BL/6 mice, due to a preferential increase in the CD8+ subpopulation. Following activation of the resting T cells with Concanavalin A (Con A), F-actin depolymerized in cells from young mice for 2 min, followed by rapid polymerization, reaching a plateau 200% above resting levels. In cells from 15-17-month-old mice, an attenuated depolymerization phase was seen for 45 sec, followed by little polymerization. No depolymerization or polymerization phases occurred in cells from aged mice. Phorbol 12 myristate 13-acetate (PMA), which activates protein kinase C (PKC), bypassing receptor mediated signals, induced actin polymerization to 57% of the levels of that after Con A stimulation in cells from both young and old animals and partially eliminated the differences in actin filament assembly due to age. Perturbation of the cytoskeleton with cytochalasin E (CE) potentiated proliferation of Con A-stimulated T cells from aged mice but did not completely restore the deficit attributed to immunosenescence. The results show an age-related impairment of cytoskeletal functions and suggest that differences in early signal transduction events contribute to the decrements in surface receptor motility and subsequent proliferation of T lymphocytes from older individuals.