Age-related impairment of early and late events of signal transduction in mouse immune cells.
The effects of aging were studied on both early and late [subsequent to activation of protein kinase C (PKC)] events of signal transduction in mouse T cell subsets. Aged C57Bl/6 mice showed significant suppression of Con A-stimulated Ca2+ mobilization in both CD4+ and CD8+T cells compared to young mice. When early signaling was bypassed by stimulating cells with the combination of a calcium ionophore and a phorbol ester. [3H]thymidine incorporation was comparable between young and aged mice while Con A-stimulated [3H]thymidine uptake remained depressed in aged mice. These results suggest that impairment of early (but not late) events may be responsible for the suppression of T cell proliferation in aged animals. Further, aged mice exhibited a significant increase in spontaneous proliferation resulting in a robust reduction of the stimulation index of both Con A and PMA/A23187-induced proliferation. Similarly, aged mice exhibited a significant increase in spontaneous IL-2R expression in both CD4+ and CD8+ T cells. No differences in IL-2 secretion were found between young and aged mice. The change in IL-2R expression was positively correlated with increased spontaneous proliferation. Overall these results suggest that: 1) impaired early (pre-PKC) rather than later (post-PKC) events of signaling may be responsible for poor proliferation of T cells, and 2) endogenous activation of cells related to increased level of IL-2R expression may play an important role in aging-associated immunosuppression.
Laboratory of Neuroscience, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
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D000375:Aging / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003208:Concanavalin A; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
D003208:Concanavalin A; D002118:Calcium