Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer's disease patients
Accelerated telomere erosion is associated with a declining immune function of caregivers of Alzheimer's disease patients
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DOI：
10.4049/jimmunol.179.6.4249
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发表时间：
2007-09-15
影响因子：
4.4
通讯作者：
Weng, Nan-ping
中科院分区：
文献类型：
--
作者：
Damjanovic, Amanda K.;Yang, Yinhua;Weng, Nan-ping
阿尔茨海默病患者的照顾者承受着与免疫功能下降相关的慢性压力。为了评估照顾者的心理和免疫学变化，我们比较了82名个体(41名照顾者和41名年龄和性别匹配的对照组)的抑郁症状、PBMC组成、体外激活诱导的增殖和细胞因子产生以及端粒长度和端粒酶活性。我们发现照顾者的抑郁症状显著高于对照组(p<；0.001)。相应地，照顾者在体外对刺激的反应中，T细胞增殖显著低于对照组，但免疫调节细胞因子(TNF-α和IL-10)的产生高于对照组。我们研究了这些变化对细胞复制寿命的影响，发现照料者PBMC的端粒长度显著短于对照组(分别为6.2和6.4kb，p<；0.05)，分离的T细胞和单核细胞的端粒长度也相似，照顾者的端粒磨损并不是由于PBMC中拥有T细胞亚群的更短的端粒增加所致。最后，我们发现照顾者外周血单个核细胞和T细胞的基础端粒酶活性显著高于对照组(p<；0.0001)，这表明细胞试图补偿照顾者端粒的过度丢失是失败的。这些发现表明，慢性应激与T细胞功能改变和免疫细胞加速老化有关，端粒过度丢失表明这一点。
Caregivers of Alzheimer's disease patients endure chronic stress associated with a decline of immune function. To assess the psychological and immunological changes of caregivers, we compared depressive symptoms, PBMC composition, in vitro activation-induced proliferation and cytokine production, and telomere length and telomerase activity of 82 individuals (41 caregivers and 41 age- and gender-matched controls). We found depressive symptoms were significantly higher in caregivers than in controls (p < 0.001). Correspondingly, caregivers had significantly lower T cell proliferation but higher production of immune-regulatory cytokines (TNF-alpha and IL-10) than controls in response to stimulation in vitro. We examined the impact of these changes on cellular replicative lifespan and found that caregivers had significantly shorter telomere lengths in PBMC than controls (6.2 and 6.4 kb, respectively, p < 0.05) with similar shortening in isolated T cells and monocytes and that this telomere attrition in caregivers was not due to an increase of shorter telomere possessing T cell subsets in PBMC. Finally, we showed that basal telomerase activity in PBMC and T cells was significantly higher in caregivers than in controls (p < 0.0001), pointing to an unsuccessful attempt of cells to compensate the excessive loss of telomeres in caregivers. These findings demonstrate that chronic stress is associated with altered T cell function and accelerated immune cell aging as suggested by excessive telomere loss.