Defective control of cytoplasmic calcium concentration in T lymphocytes from old mice.
Cytoplasmic calcium concentration ([Ca]i) rises within minutes of exposure of T lymphocytes to a mitogen. T cells from old mice are defective in this reaction, a defect that could reflect either altered signal transduction or instead a more general age-associated change in intracellular calcium regulation. We therefore tested the ability of T cells from old mice to regulate their [Ca]i concentration after exposure to low concentrations of ionomycin, an agent that raises [Ca]i but bypasses receptor-mediated signal transduction mechanisms. Exposure of T cells to ionomycin leads to an abrupt increase in [Ca]i followed by stabilization at a dose-dependent plateau level that is affected by extracellular EGTA, by calmodulin inhibitors, and by modulators of protein kinase C. Plateau levels of [Ca]i after ionomycin challenge were consistently lower in T cells from old mice than in T cells from young mice. Flow cytometric experiments showed that while essentially all T cells from both old and young mice responded to ionomycin, they did so to an extent that depended on donor age. The age-dependent increase in resistance to ionomycin-induced changes in [Ca]i cannot be attributed to diminished membrane permeability to the ionomycin-calcium complex. The data suggest that aging may lead, in T lymphocytes, to a relative resistance to increases in [Ca]i, a resistance that in turn prevents cell activation.
Department of Pathology, Boston University School of Medicine, Massachusetts 02118.
R A
RA
Miller
B
B
Philosophe
I
I
Ginis
G
G
Weil
B
B
Jacobson
D000375:Aging; D000818:Animals; D002118:Calcium / Q000097:blood*; D002147:Calmodulin / Q000378:metabolism; D004987:Ethers / Q000494:pharmacology; D005434:Flow Cytometry; D015759:Ionomycin; D051379:Mice; D011493:Protein Kinase C / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*
D002147:Calmodulin; D004987:Ethers; D015759:Ionomycin; D011493:Protein Kinase C; D002118:Calcium