ABSTRACT
In some systems, including lectin-mediated activation of a T cell lymphoma, generation of inositol trisphosphate by hydrolysis of phosphatidylinositol-bisphosphate is thought to mediate much of the early increase in Cai from the endoplasmic reticulum. The authors test T cells from old mice to see whether they would proliferate when exposed to PMA (1 ng/ml) and the ionophore ionomycin. They find that these intracellular mediators could largely overcome the age-related proliferative defect observed in cells stimulated with Con-A. T cells from old mice exhibit deficits very early in the sequence of events by which extracellular activators (e.g., plant lectins and antibodies to the T cell receptor) induce DNA synthesis and eventual mitosis. The importance of early deficits in transmembrane signal transductions is suggested by the ability of T cells from old mice to proliferate well when stimulated by a combination of phorbol ester and calcium ionophore that together bypass the requirement for reception of extracellular signals.
