Age-dependent signature of metallothionein expression in primary CD4 T cell responses is due to sustained zinc signaling.
Age-dependent signature of metallothionein expression in primary CD4 T cell responses is due to sustained zinc signaling.
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DOI：
10.1089/rej.2008.0747
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发表时间：
2008-12
影响因子：
2.6
通讯作者：
Goronzy JJ
中科院分区：
文献类型：
--
作者：
Lee WW;Cui D;Czesnikiewicz-Guzik M;Vencio RZ;Shmulevich I;Aderem A;Weyand CM;Goronzy JJ
对疫苗接种和病毒感染产生适应性免疫反应的能力随着年龄的增长而下降。为了确定导致免疫衰老的机制，研究人员对60- 75岁无明显功能缺陷的个体进行了原发性CD4 T细胞反应检测。转录组分析表明锌稳态存在选择性缺陷。CD4 T细胞活化与锌通过锌转运蛋白Zip6内流相关，导致游离细胞质锌增加和负反馈回路的激活，包括锌结合金属硫蛋白的诱导。在年轻人中，激活诱导的细胞质锌浓度在2天后下降到低于刺激前的水平。相比之下，老年个体活化的naïve CD4 T细胞未能下调胞质锌，导致金属硫蛋白过度诱导。激活诱导的金属硫蛋白调节活化T细胞的氧化还原状态，并解释了老年CD4 T细胞增殖的增加，这表明T细胞锌稳态的调节是一种代偿机制，可以随着年龄的增长保持naïve CD4 T细胞的复制潜力。
The ability to mount adaptive immune responses to vaccinations and viral infections declines with increasing age. To identify mechanisms leading to immunosenescence, primary CD4 T cell responses were examined in 60- to 75-year-old individuals lacking overt functional defects. Transcriptome analysis indicated a selective defect in zinc homeostasis. CD4 T cell activation was associated with zinc influx via the zinc transporter Zip6, leading to increased free cytoplasmic zinc and activation of negative feedback loops, including the induction of zinc-binding metallothioneins. In young adults, activation-induced cytoplasmic zinc concentrations declined after 2 days to below prestimulation levels. In contrast, activated naïve CD4 T cells from older individuals failed to downregulate cytoplasmic zinc, resulting in excessive induction of metallothioneins. Activation-induced metallothioneins regulated the redox state in activated T cells and accounted for an increased proliferation of old CD4 T cells, suggesting that regulation of T cell zinc homeostasis functions as a compensatory mechanism to preserve the replicative potential of naïve CD4 T cells with age.
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影响因子：
--
作者：
DONAHUE, JG;CHOO, PW;PLATT, R
通讯作者：
PLATT, R
影响因子：
4.4
作者：
Garcia, Gonzalo G.;Akha, Amir A. Sadighi;Miller, Richard A.
通讯作者：
Miller, Richard A.
影响因子：
4.4
作者：
Hadrup, SR;Strindhall, J;Wikby, A
通讯作者：
Wikby, A
影响因子：
5.4
作者：
Goronzy, JJ;Fulbright, JW;Weyand, CM
通讯作者：
Weyand, CM
影响因子：
64.8
作者：
Douek, DC;McFarland, RD;Koup, RA
通讯作者：
Koup, RA