Impact of post-thymic cellular longevity on the development of age-associated CD4+ T cell defects
Impact of post-thymic cellular longevity on the development of age-associated CD4+ T cell defects
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DOI：
10.4049/jimmunol.180.7.4465
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发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Swain, Susan L.
中科院分区：
文献类型：
--
作者：
Jones, Stephen C.;Clise-Dwyer, Karen;Swain, Susan L.
由于细胞免疫反应下降和不道德，老年人感染的风险更高。这种功能障碍的核心是初始CD4(+) T细胞区室的反应性降低。我们实验室以前的数据表明，尽管在最近的胸腺移民人群中，老年幼稚CD4(+) T细胞反应的缺陷是明显的，但在胸腺后的外围延长寿命期间，会出现额外的缺陷。为了进一步研究导致衰老缺陷的因素，我们采用OT-II tcr转基因（Tg）小鼠模型。我们发现，由于衰老的OT-II小鼠外周的幼稚V β 5(+) Tg CD4(+) T细胞的超抗原介导的明显损失，该隔室变得丰富，用于减少胸腺后寿命的细胞，导致老年小鼠近期胸腺迁移的频率与年轻小鼠相似。对胸腺后寿命降低的衰老OT-II细胞的纯化和功能分析表明，在体外对Ag的反应中，它们的扩张和IL-2的产生与年龄相关。然而，这些细胞的体内扩增、IL-2产生和同源B细胞辅助能力与幼年小鼠的细胞相似。相比之下，老龄HNT - Tg小鼠的T细胞在体外和体内模型中表现出延长的胸腺后寿命，并表现出严重的缺陷。这些数据支持增加胸腺后寿命的需求与最严重的初始CD4(+) T细胞老化缺陷的发展之间的相关性。
Elderly people are at higher risk for infections due to declining cellular and Immoral immune responses. Central to this dysfunction is the reduced responsiveness of the naive CD4(+) T cell compartment. Previous data from our laboratory suggest that although defects in the aged naive CD4(+) T cell response are apparent in recent thymic emigrant populations, additional defects develop during extended post-thymic longevity in the periphery. To further investigate the factors that lead to aging defects, we took advantage of the OT-II TCR-transgenic (Tg) mouse model. We show that because of an apparent superantigen-mediated loss of naive V beta 5(+) Tg CD4(+) T cells from the periphery of aging OT-II mice, this compartment becomes enriched for cells of reduced post-thymic longevity, resulting in a frequency of recent thymic emigrants in aged mice that is similar to that of young mice. Purification and functional analysis of aged OT-II cells with reduced post-thymic longevity reveal that they have an age-associated decrease in expansion and IL-2 production in response to Ag in vitro. However, the in vivo expansion, IL-2 production, and cognate B cell helper ability of these cells are similar to those of cells from young mice. In contrast, T cells from aged HNT Tg mice demonstrate extended post-thymic longevity and exhibit severe defects in the same in vitro and in vivo models. These data support a correlation between the requirement for increased post-thymic longevity and the development of the most severe naive CD4(+) T cell-aging defects.