Defective calcium signal generation in a T cell subset that accumulates in old mice.
Table 2 outlines our current understanding of the bases for activation defects in T cells from old mice, with speculative ideas indicated by a question mark. Many, though not all, T cells from old mice show defects in the generation of Ca2+ signals within the first few minutes of exposure to a mitogenic lectin or to antibody to components of the T cell receptor. These defects seem to involve an increased resistance to changes in cytoplasmic free calcium ion concentration, perhaps though changes in the calcium extrusion pump. Diminished rates of uptake of calcium from extracellular sources also contribute to defective calcium signal generation. Some aspects of the activation process, including production of inositol phosphates, seem in contrast not to be altered by aging in mice. T cells with defects in Ca2+ responses seem to be contained preferentially within the PGP-1hi subsets of both the helper and cytotoxic lineages, subsets that accumulate dramatically in old mice. Since the PGP-1hi phenotype is thought to distinguish memory T cells from virgin thymic emigrants, we propose a model in which aging leads to the progressive conversion of virgin to memory T cells, which in turn gradually lose the ability to respond to activating stimuli.
Miller
R A
RA
Department of Pathology, Boston University School of Medicine, Massachusetts 02118.
D000375:Aging / Q000276:immunology*; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002118:Calcium / Q000378:metabolism*; D003208:Concanavalin A / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D016201:Receptors, Lymphocyte Homing; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000954:Antigens, Surface; D016201:Receptors, Lymphocyte Homing; D003208:Concanavalin A; D002118:Calcium