Diminished calcium signal generation in subsets of T lymphocytes that predominate in old mice.
We have recently demonstrated an age-dependent increase in the fraction of murine T cells that express high levels of the Pgp-1 surface glycoprotein, thought to be a marker for memory lymphocytes. T cells from old mice also exhibit a defect in the generation of cytoplasmic calcium signals after stimulation with Con A. To see if the increase in Pgp-1+ T cells could account for defective calcium signal generation in old mice, we carried out flow cytometric analyses to examine calcium signal production in T cells expressing high or low levels of the Pgp-1 marker. We report here that Pgp-1+ T cells, from both old and young mice, do indeed generate relatively poor Ca2+ responses when exposed either to receptor-dependent mitogens (e.g., Con A and anti-CD3) or to activators like ionomycin that bypass receptor-mediated signal transduction pathways. Both CD4 (helper) and CD8 (killer) T cells show poor calcium responses. These data suggest that the shift, with age, toward Pgp-1+ T cells, which are relatively refractory to stimuli that raise intracellular calcium concentrations, may contribute to poor cell-mediated immune function in old animals.
Philosophe
B
B
Boston University School of Medicine.
Miller
R A
RA
D000375:Aging / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000954:Antigens, Surface / Q000032:analysis; D017252:CD3 Complex; D002118:Calcium / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016201:Receptors, Lymphocyte Homing; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D016201:Receptors, Lymphocyte Homing; D003208:Concanavalin A; D015759:Ionomycin; D002118:Calcium