No abstract

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.

Blastogenic responses to T- and B-lymphocyte mitogens were tested in suspensions of splenocytes from 15- and 24- to 28-mo-old C57BL/6 mice and compared with analogous responses in young animals. The mice were housed under constant environmental conditions with alternating light-dark cycles (LD 12:12). Single cell suspensions were cultured in vitro with mitogens, and the induced incorporation of tritiated thymidine by dividing cells was determined. Increases in periodicity of responses to concanavalin A and phytohemagglutinin by T cells and to lipopolysaccharide by B cells and lower mean levels of activation characterized rhythms in cells from 15-mo-old and senescent mice compared with young animals. Amplitudes of the rhythms were unchanged at 15 mo, but by 24 mo of age rhythmic responses of T but not B cells were damped. The separable effects of age on expression of circannual rhythms by T and B lymphocytes suggest another mechanism for imbalance in the immune system. Phases of depressed responses that are extended for several months in populations of older mice could provide increased opportunities for environmental assaults.