Maladaptation to mental stress mitigated by the adaptive immune system via depletion of naturally occurring regulatory CD4+CD25+cells
Maladaptation to mental stress mitigated by the adaptive immune system via depletion of naturally occurring regulatory CD4+CD25+cells
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DOI：
10.1002/neu.20249
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发表时间：
2006-05-01
期刊：
影响因子：
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通讯作者：
Kipnis, Jonathan
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文献类型：
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作者：
Cohen, Hagit;Ziv, Yaniv;Kipnis, Jonathan
外周细胞免疫最近被证明在大脑可塑性和性能中起着关键作用。然而，没有研究参与的T细胞的抗原特异性，也没有研究它们与心理压力的相关性。在这里，我们表明，使用小鼠模型，适应性免疫减轻适应不良的急性心理压力，已知触发异常行为，让人想起人类创伤后应激障碍。在暴露于捕食者气味后，对小鼠的行为适应（通过声惊吓反应和回避行为测量）进行评估，发现T细胞缺陷小鼠中的适应不良比野生型小鼠中的适应不良要多几倍。一个单一的群体的T细胞反应中枢神经系统（CNS）相关的自身蛋白是足够的，赋予免疫缺陷小鼠的能力，以承受心理压力。发现天然存在的CD4+CD25+调节性T细胞抑制这种内源性抗应激属性。这些发现表明，对大量表达的CNS抗原特异性的T细胞负责脑组织的稳态，并帮助个体科普紧张的生活事件。他们还可能为开发基于免疫的精神疾病疗法指明了方向，该疗法基于上调与自身抗原部分交叉反应的T细胞或减弱调节性T细胞的活性。(c)2006 Wiley Periodicals，Inc.
Peripheral cellular immunity was recently shown to play a critical role in brain plasticity and performance. The antigenic specificity of the participating T cells, however, was not investigated, and nor was their relevance to psychological stress. Here we show, using a mouse model, that adaptive immunity mitigates maladaptation to the acute psychological stress known to trigger abnormal behaviors reminiscent of human post-traumatic stress disorder. Assessment of behavioral adaptation (measured by the acoustic startle response and avoidance behavior) in mice after their exposure to predator odor revealed that maladaptation was several times more prevalent in T cell-deficient mice than in their wildtype counterparts. A single population of T cells reactive to central nervous system (CNS)-associated self-protein was sufficient to endow immune-deficient mice with the ability to withstand the psychological stress. Naturally occurring CD4+CD25+ regulatory T cells were found to suppress this endogenous anti-stress attribute. These findings suggest that T cells specific to abundantly expressed CNS antigens are responsible for brain tissue homeostasis and help the individual to cope with stressful life episodes. They might also point the way to development of immune-based therapies for mental disorders, based either on upregulation of T cells that partially cross-react with self-antigens or on weakening of the activity of regulatory T cells. (c) 2006 Wiley Periodicals, Inc.