Attenuation of the cytotoxic T lymphocyte response to lymphocytic choriomeningitis virus in mice subjected to chronic social stress
Attenuation of the cytotoxic T lymphocyte response to lymphocytic choriomeningitis virus in mice subjected to chronic social stress
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DOI：
10.1016/j.bbi.2010.10.016
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发表时间：
2011-02
期刊：
影响因子：
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通讯作者：
Annette Sommershof;Michael Basler;C. Riether;H. Engler;M. Groettrup
中科院分区：
文献类型：
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作者：
Annette Sommershof;Michael Basler;C. Riether;H. Engler;M. Groettrup
慢性应激被怀疑会增加感染的易感性，但来自生理应激模型的实验证据很少。我们研究了慢性社会应激对淋巴细胞性脉络丛脑膜炎病毒（LCMV）感染小鼠后病毒特异性CTL应答的影响。在感染前连续六天经受社会应激的小鼠显示出产生IFN-γ的TCD 8+脾细胞的显著减少和IFN-γ的血浆浓度的显著降低。与此相反，LCMV特异性CTL反应的产生并没有改变在小鼠经历相同的压力程序同时感染。此外，LCMV感染前6天和感染后3天的应激暴露显著降低了脾脏中TCD 8+细胞的扩增，这是由于体内增殖减少。糖皮质激素受体的药理学阻断完全消除了TCD 8+扩张的应激相关下降。应激小鼠显示早期T细胞活化标志物CD 69的表达显著降低，以及IFN-γ和IL-2的体外细胞因子分泌受损。此外，社会压力导致TCD 8+细胞的迁移能力改变，如过继性T细胞转移实验所示。总之，这项研究表明，慢性社会压力从根本上抑制了病毒感染期间T细胞的功能能力。
Chronic stress is suspected to increase the susceptibility to infections but experimental evidence from physiological stress models is scarce. We examined the effects of chronic social stress on virus-specific CTL responses in mice after infection with lymphocytic choriomeningitis virus (LCMV). Mice subjected to social stress on six consecutive days prior to infection showed a significant reduction of IFN-γ producing TCD8+splenocytes and markedly lowered plasma concentrations of IFN-γ. In contrast, the generation of LCMV-specific CTL responses was not altered in mice undergoing the same stress procedure concurrently with infection. Furthermore, stress exposure 6days before and additional 3days after LCMV infection profoundly reduced the expansion of TCD8+cells in the spleen, due to diminished in vivo proliferation. Pharmacological blockade of glucocorticoid receptors completely abrogated the stress-associated decline of TCD8+expansion. Stressed mice showed a significantly reduced expression of the early T-cell activation marker CD69 as well as impaired in vitro cytokine secretion of IFN-γ and IL-2. Additionally, social stress led to an altered migration capacity of TCD8+cells as demonstrated by adoptive T cell transfer experiments. Taken together, this study shows that chronic social stress fundamentally suppresses the functional capacities of T cells during a viral infection.