Impaired phorbol ester and calcium ionophore induced proliferation of T cells from old humans.
Current models of T cell activation implicate increases in intracellular free Ca2+ concentration and activation of the Ca2+ and phospholipid dependent enzyme protein kinase C (PKC) as important early events leading to interleukin 2 (IL-2) production, interleukin 2 receptor (IL-2R) expression, and subsequent cell proliferation. The present study examined the age-related defect in T cell proliferation to determine if signals that activate PKC and increase intracytosolic free Ca2+ concentration might be defective. Using phorbol myristate acetate (PMA), which directly activates PKC, and Ca2+ ionophore A23187, which increases intracellular cytoplasmic free Ca2+ concentration, the induction of IL-2 secretion, IL-2R expression and cell proliferation were studied. The results demonstrate that following stimulation with PMA and A23187, purified T cells from elderly subjects demonstrate low levels of IL-2 production, IL-2R expression and cell proliferation. Exogenous purified human IL-2 did not fully correct the low proliferative responses of T cells from old donors, however, did markedly boost the response. While it appears that the inability of T cells to express IL-2R and respond to IL-2, along with a lower endogenous IL-2 production are limiting factors in cell proliferation, the inability of PMA and A23187 to correct this defect suggests that the early phases of signal transduction per se are probably not a primary cause of the immunodeficiency seen in ageing.
D000328:Adult; D000368:Aged; D000375:Aging / Q000276:immunology*; D000001:Calcimycin / Q000494:pharmacology*; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000032:analysis; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D000001:Calcimycin; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine