CD4-Positive T Lymphocytes Provide a Neuroimmunological Link in the Control of Adult Hippocampal Neurogenesis
CD4-Positive T Lymphocytes Provide a Neuroimmunological Link in the Control of Adult Hippocampal Neurogenesis
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DOI：
10.4049/jimmunol.0801218
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发表时间：
2009-04-01
影响因子：
4.4
通讯作者：
Kempermann, Gerd
中科院分区：
文献类型：
--
作者：
Wolf, Susanne A.;Steiner, Barbara;Kempermann, Gerd
成人海马神经发生发生在一个特殊的宽容的微环境。神经免疫学机制可能主要涉及控制成人神经发生基线水平的内源性自我平衡原则。我们在这项研究中表明，这种稳态部分依赖于CD 4阳性T淋巴细胞。系统性耗竭CD 4阳性T淋巴细胞导致海马神经发生显著减少，Morris水迷宫中的逆转学习受损，脑中脑源性神经营养因子表达降低。未观察到CD 8或B细胞的这种作用。RAG 2（-/-）小鼠用CD 4细胞而不是用CD 8细胞再增殖再次增加了前体细胞增殖。我们实验中的T细胞是非CNS特异性的，在健康大脑中很少检测到。因此，我们可以排除免疫细胞和脑细胞之间的细胞-细胞接触或淋巴细胞浸润到CNS中作为效应的先决条件。CD 4-T细胞对神经发生的影响。我们认为，系统性CD 4-T细胞活性是维持成人海马细胞可塑性所必需的，并代表了大脑对环境变化做出反应的进化相关通信途径。免疫学杂志，2009，182：3979-3984.
Adult hippocampal neurogenesis occurs in an exceptional permissive microenvironment. Neuroimmunological mechanisms might be prominently involved in the endogenous homeostatic principles that control baseline levels of adult neurogenesis. We show in this study that this homeostasis is partially dependent on CD4-positive T lymphocytes. Systemic depletion of CD4-positive T lymphocytes led to significantly reduced hippocampal neurogenesis, impaired reversal learning in the Morris water maze, and decreased brain-derived neurotrophic factor expression in the brain. No such effect of CD8 or B cells was observed. Repopulation of RAG2(-/-) mice with CD4, but not with CD8 cells again increased precursor cell proliferation. The T cells in our experiments were non-CNS specific and rarely detectable in the healthy brain. Thus, we can exclude cell-cell contacts between immune and brain cells or lymphocyte infiltration into the CNS as a prerequisite for an effect. of CD4-T cells on neurogenesis. We propose that systemic CD4-T cell activity is required for maintaining cellular plasticity in the adult hippocampus and represents an evolutionary relevant communication route for the brain to respond to environmental changes. The Journal of Immunology, 2009, 182: 3979-3984.