Miller R A
J Immunol. 1986 Aug 1;137(3):805-8.
Current models for lectin-induced T cell proliferation suggest that activation of protein kinase C (PK-C) and elevation of cytoplasmic Ca2+ may both play important roles in the earliest phases of signal transduction. To learn more about the relative inability of T cells from old mice to proliferate in response to mitogenic stimuli, we attempted to stimulate T cells by the synergistic effects of a PK-C activator, phorbol myristate acetate (PMA), and the calcium ionophore ionomycin. T cells from young mice respond as well to optimal combinations of these agents as they do to the strong polyclonal activator Con A, but T cells from old mice respond much better to PMA plus ionomycin than they do to Con A. This result suggests that an inability to transduce the signal supplied by extracellular ligands into the intracellular signals represented by Ca2+ and PK-C activators may underlie the age-associated loss of T cell reactivity. We also found evidence for a second defect in old T cells related to their response to elevated intracellular Ca2+: old T cells, compared with young, required higher levels of ionomycin for maximal proliferation.
目前关于凝集素诱导的T细胞增殖模型表明，蛋白激酶C（PK-C）的激活以及细胞质中Ca2+水平的升高在信号转导的最初阶段可能都起着重要作用。为了更深入了解老年小鼠T细胞对促有丝分裂刺激反应性相对降低的情况，我们尝试通过PK-C激活剂佛波酯肉豆蔻酸酯乙酸酯（PMA）和钙离子载体离子霉素的协同作用来刺激T细胞。年轻小鼠的T细胞对这些试剂的最佳组合的反应与它们对强多克隆激活剂刀豆蛋白A（Con A）的反应一样好，但老年小鼠的T细胞对PMA加离子霉素的反应比对Con A的反应要好得多。这一结果表明，无法将细胞外配体提供的信号转导为以Ca2+和PK-C激活剂为代表的细胞内信号，可能是与年龄相关的T细胞反应性丧失的基础。我们还发现老年T细胞对细胞内Ca2+升高反应存在第二个缺陷的证据：与年轻T细胞相比，老年T细胞需要更高水平的离子霉素才能实现最大程度的增殖。
