Modulation of human lymphocyte proliferative response with aging
Modulation of human lymphocyte proliferative response with aging
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DOI：
10.1016/s0531-5565(01)00204-2
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发表时间：
2002-01-01
影响因子：
3.9
通讯作者：
Fulop, T
中科院分区：
文献类型：
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作者：
Douziech, N;Seres, L;Fulop, T
以前，我们已经证明了跨膜信号的年龄相关的变化。随着年龄的增长，免疫应答中发现的最可重复的变化之一是在各种不同的有丝分裂原刺激下淋巴细胞增殖的减少。在这里，我们证实，与植物血凝素（PHA），重组人IL-2，或抗CD 3单克隆抗体刺激的增殖反应都是更大的年轻（20-25岁）比老年人（60-87岁）人口。我们尝试使用作用于不同水平的跨膜信号传导（百日咳毒素、霍乱毒素、异丙肾上腺素、PMA、Ca离子载体A23187）以及淋巴细胞质膜水平（甲基-β-环糊精，MBCD）的各种试剂或通过使用抗氧化维生素（维生素E或Q）来调节增殖反应。这些药物都不能有效地恢复淋巴细胞的增殖反应从老年人的年轻人的水平。即使A23187和PMA直接作用于钙代谢和蛋白激酶C活性的组合也不足以恢复老年受试者T细胞的促有丝分裂能力降低。环糊精，这降低了膜的胆固醇含量，增加了老年人的淋巴细胞的增殖反应，但不是年轻人的水平。维生素E在两个年龄组中对淋巴细胞刺激有非常强的抑制作用，除了与老年人T细胞中的MBCD组合，而维生素C没有显着的调节作用。在抗CD 3单抗刺激后，发现T细胞中MAPK ERK和p38活化随着老化而降低。维生素E而不是维生素C强烈抑制MAPK ERK或p38活化。某些分子的直接激活或膜胆固醇含量的调节似乎是有效的免疫调节干预衰老。(C)2002年爱思唯尔科技有限公司All rights reserved.
Previously, we have demonstrated age-associated alterations in transmembrane signaling. One of the most reproducible alterations found in the immune response with aging is the decrease of lymphocyte proliferation on stimulation with various different mitogens. Here, we confirm that proliferative responses to stimulation with phytohaemagglutin (PHA), recombinant human IL-2, or anti-CD3 monoclonal antibody are all greater in the young (20-25 years) than old (60-87 years) population. We attempted to modulate the proliferative response using various agents acting at different levels of transmembrane signaling (pertussis toxin, cholera toxin, isoproterenol, PMA, Ca ionophore A23187), as well as at the level of the lymphocyte plasma membrane (methyl-p-cyclodextrin, MBCD), or by using antioxidant vitamins (Vitamin E or Q. None of these agents was able to restore effectively the proliferative response of lymphocytes from the aged to the level of young subjects. Even the combination of A23187 and PMA acting directly on calcium metabolism and protein kinase C activity was insufficient to restore the decreased mitogenic capacity of T cells from elderly subjects. Cyclodextrin, which decreases the cholesterol content of the membrane, increased the proliferative response of lymphocytes of elderly subjects, but not to the level of the young. Vitamin E had a very strong inhibitory effect on lymphocyte stimulation in both the age groups, except in combination with MBCD in T cells of the elderly, while Vitamin C had no significant modulatory effect. MAPK ERK and p38 activation was found to be decreased with aging in T cells after anti-CD3 mAb stimulation. Vitamin E but not Vitamin C strongly inhibited MAPK ERK or p38 activation. The direct activation of certain molecules or the modulation of the cholesterol content of the membrane seems to be effective immunomodulatory interventions with aging. (C) 2002 Elsevier Science Inc. All rights reserved.