Intracellular free Ca2+ fluxes and responses to phorbol ester in T lymphocytes from healthy elderly subjects.

A group of healthy elderly subjects (greater than or equal to 75 years) was selected by the strict criteria of the SENIEUR protocol, and compared with healthy young (less than or equal to 35 years) volunteers. Mitogenic responses of peripheral blood mononuclear cells to phytohaemagglutinin and anti-CD3 were significantly reduced in the elderly (P less than 0.0002), thereby confirming that even though in perfect health, elderly individuals show impaired cell-mediated immunity. However, no abnormality of intracellular free Ca2+ fluxes could be detected in purified T cells from the elderly subjects when stimulated with anti-CD3 antibody. Nevertheless, both the proliferative responses of purified T cells to phorbol ester and calcium ionophore (Ionomycin) and the phorbol ester-induced inhibition of the Ca2+ response were defective in the elderly subjects (P less than 0.003 and P less than 0.0002, respectively). These data suggest that signal transduction and the generation of second messengers proceed normally in T cells from the elderly, but downstream events mediated by activation of protein kinase C are dysfunctional.