Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections.
Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections.
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面对潜在的持续感染，老化和终身维持T细胞子集。
DOI：
10.1038/nri2318
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发表时间：
2008-07
期刊：
影响因子：
--
通讯作者：
Nikolich-Zugich J
中科院分区：
文献类型：
--
作者：
Nikolich-Zugich J
T细胞免疫力下降是老年人最持久和最严重的缺陷之一。对这种下降的治疗性纠正通常会恢复免疫应答和免疫防御。老年人的T细胞免疫下降至少有两个基础：幼稚T细胞对刺激的反应性下降（细胞自主缺陷）和幼稚T细胞数量和多样性减少，导致记忆T细胞池占主导地位（T细胞群体失衡）。本文讨论了与年龄相关的T细胞群体失衡的两个关键原因：外周T细胞库的稳态循环或增殖性扩张，以及潜伏的持续感染，这些感染在个体的一生中反复刺激T细胞库。胸腺产生幼稚T细胞的减少迫使衰老的生物体依赖于代偿性稳态机制来维持幼稚和记忆T细胞库之间的平衡。虽然这可能最初是成功的，但最近的证据表明，在生命的后期，这些机制耗尽了它们的有用性，实际上有助于剩余的幼稚T细胞的进一步死亡。潜伏性持续感染，特别是疱疹病毒，导致免疫系统的终身周期性再刺激，在这里，病毒再激活的作用，使用疱疹病毒感染和衰老的小鼠模型的再刺激的证据。相对角色和自我平衡和病毒因子之间的相互作用进行了讨论，前者具有令人惊讶的突出作用。最后，根据我们知识的这些进步，对免疫复兴和抗衰老干预的模式进行了辩论。T细胞免疫力下降是老年人感染性疾病发病率和死亡率的主要原因。扬科·尼科利奇-鲁鲁吉奇（Janko Nikolich-Jugich）权衡了免疫衰老中稳态因子和持久性病毒之间的相对作用和相互作用。多样化和平衡良好的T细胞库被认为是有效防御新的或重新出现的病原体感染的关键。在哺乳动物生命的最后三分之一，由于T细胞产生和消耗的变化，维持平衡的T细胞库变得非常具有挑战性。在这篇综述中，我质疑潜在的持续性病原体是否可能是导致这种不平衡的关键因素，以及它们是否决定了年龄相关免疫缺陷的程度。
A decline in T-cell immunity is one of the most consistent and most profound deficiencies of the elderly. Therapeutic correction of this decline often restores immune responsiveness and immune defence. T-cell immune decline in the elderly has at least two underpinnings: a drop in the responsiveness of naive T cells to stimulation (cell-autonomous defects) and a reduction in naive T-cell numbers and diversity that leads to a dominant memory T-cell pool (T-cell population imbalance). This article discusses two key causes of age-related T-cell population imbalance: homeostatic cycling or proliferative expansion in the peripheral T-cell pool, and latent persistent infections, which repeatedly stimulate the T-cell pool over the lifetime of the individual. The reduction in production of naive T cells by the thymus forces the ageing organism to rely on compensatory homeostatic mechanisms to maintain the balance between naive and memory T-cell pools. Although this may be initially successful, recent evidence suggests that late in life these mechanisms exhaust their usefulness and actually contribute to a further demise of the remaining naive T cells. Latent persistent infections, particularly with herpesviruses, lead to life-long periodic restimulation of the immune system, here, evidence is presented for the role of viral reactivation in this restimulation using a mouse model of herpesvirus infection and ageing. Relative roles and the interplay between the homeostatic and viral factors are discussed, with the former having a surprisingly prominent role. Finally, modes of immune rejuvenation and anti-ageing intervention are debated in light of these advances in our knowledge. A decline in T-cell immunity is a major cause of morbidity and mortality from infectious diseases in the elderly. Janko Nikolich-Žugich weighs up the relative roles of and the interplay between homeostatic factors and persistent viruses in immune senescence. A diverse and well-balanced repertoire of T cells is thought to be crucial for the efficacious defence against infection with new or re-emerging pathogens throughout life. In the last third of the mammalian lifespan, the maintenance of a balanced T-cell repertoire becomes highly challenging because of the changes in T-cell production and consumption. In this Review, I question whether latent persistent pathogens might be key factors that drive this imbalance and whether they determine the extent of age-associated immune deficiency.
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胸腺和最近的胸腺移民在维持成年外周淋巴细胞库中的作用。
影响因子：
15.3
作者：
Berzins, S P;Boyd, R L;Miller, J F
通讯作者：
Miller, J F
DOI：
10.1073/pnas.96.17.9787
发表时间：
1999-08-17
影响因子：
11.1
作者：
Berzins, SP;Godfrey, DI;Boyd, RL
通讯作者：
Boyd, RL
影响因子：
5.5
作者：
Betts, RF;Treanor, JJ
通讯作者：
Treanor, JJ
影响因子：
15.3
作者：
Casazza, Joseph P.;Betts, Michael R.;Price, David A.;Precopio, Melissa L.;Ruff, Laura E.;Brenchley, Jason M.;Hill, Brenna J.;Roederer, Mario;Douek, Daniel C.;Koup, Richard A.
通讯作者：
Koup, Richard A.
影响因子：
20.3
作者：
Brenchley, JM;Karandikar, NJ;Koup, RA
通讯作者：
Koup, RA