Aging-related deficiency in intracellular calcium response to anti-CD3 or concanavalin A in murine T-cell subsets.
To examine whether intracellular free calcium ([Ca2+]i) signals are reduced in murine T-lymphocyte subsets in aging, we used a flow cytometric assay with the dye indo-I and simultaneous immunofluorescence. Calcium response was reduced in both CD4+ and CD8+ subsets, after stimulation with concanavalin A or anti-CD3 monoclonal antibody over a broad range of concentrations. Experiments carried out in the presence of EGTA indicate that both calcium mobilization from internal stores and extracellular calcium influx were reduced. The reduced overall response was in part due to a decreased number of responding cells in aged animals. In contrast, the [Ca2+]i response produced by the crosslinking of Thy1 and Ly1 (CD5) surface molecules did not show significant differences between young and old mice, indicating that some signaling mechanisms are intact in aged animals. These data also suggest that there are substantial differences between humans and mice in age-related changes in signal transduction.
Grossmann
A
A
Department of Pathology, University of Washington, Seattle.
Ledbetter
J A
JA
Rabinovitch
P S
PS
D000375:Aging / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D003208:Concanavalin A; D002118:Calcium