Age-related events in human active T lymphocytes: changes in the phosphoinositidase C activity

Since PHA-stimulated active T lymphocytes from aged humans showed changes in the metabolic pattern of inositol lipids in comparison with young subjects, we studied the possible role of phosphoinositidase C (PIC) in the generation of this phenomenon. The breakdown of exogenous [3H]phosphatidylinositol 4,5-bisphosphate was found to be optimal at neutral pH and Ca++ concentrations close to millimolar levels. Under these conditions PIC activity of resting lymphocytes did not differ in aged and young subjects, while, after short periods of PHA stimulation (up to 4 hr) the substrate hydrolysis was lower and delayed in the elderly group in comparison with that of controls. Our findings support the hypothesis that the age-related default of this enzyme, responsible for the age-related changes in the inositol lipid pathway of this peculiar subpopulation, could be involved, as a primary event, in the mechanisms leading to the reduced proliferative response of aged active T lymphocytes.