The adoptive transfer of BCG-induced T lymphocytes contributes to hippocampal cell proliferation and tempers anxiety-like behavior in immune deficient mice
The adoptive transfer of BCG-induced T lymphocytes contributes to hippocampal cell proliferation and tempers anxiety-like behavior in immune deficient mice
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BCG 诱导的 T 淋巴细胞的过继转移有助于海马细胞增殖并减轻免疫缺陷小鼠的焦虑样行为
DOI：
10.1371/journal.pone.0225874
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发表时间：
2020-04-02
期刊：
影响因子：
3.7
通讯作者：
Yao, Zhibin
中科院分区：
文献类型：
--
作者：
Song, Dan;Qi, Fangfang;Yao, Zhibin
我们以前曾报道，新生儿卡介苗(BCG)接种通过影响脑内的神经免疫环境来改善早期神经发生和行为，但T淋巴细胞的激活表型和功能变化是否影响脑发育尚不确定。在这里，我们通过过继转移BALB/c野生型小鼠的T淋巴细胞到幼鼠体内来研究卡介苗接种的效果。我们的结果表明，过继卡介苗诱导的淋巴细胞(BCG->；幼稚小鼠)在完成高架加迷宫(EPM)测试时表现出抗焦虑和抗抑郁的表现。与此同时，与PBS->；幼鼠和裸鼠相比，BCG->；幼鼠在海马区拥有更多的细胞增殖和新生神经元。卡介苗幼鼠血清中干扰素-γ和IL-4水平升高，而肿瘤坏死因子-α和IL-1β水平降低。我们进一步发现，卡介苗-GT；幼小鼠脾中CD_4~+和CD_8~+T细胞对幼稚细胞(CD62L+CD44low)、效应记忆细胞(CD62L−CD44hi)、中枢记忆细胞(CD62L+CD44hi)和急性/激活效应细胞(CD62L−CD44low)表现出不同的再分配。重要的是，卡介苗诱导的T淋巴细胞过继转移进入了裸鼠的硬脑膜和脑实质。T淋巴细胞的激活表型和功能改变很可能影响脑内的神经免疫环境，而脾中CD4+和CD8+记忆T细胞比例的变化可能影响血清中相关细胞因子的表达，这是我们的行为结果的原因。因此，我们得出结论，卡介苗诱导的T淋巴细胞过继转移有助于免疫缺陷小鼠的海马细胞增殖和缓解焦虑样行为。我们的工作表明，卡介苗接种改善了海马细胞的增殖结果和行为，这可能是由于脾效应/记忆T淋巴细胞调节大脑中的神经免疫利基。
We previously have reported that neonatal Bacillus Calmette-Guerin (BCG) vaccination improves neurogenesis and behavior in early life through affecting the neuroimmune milieu in the brain, but it is uncertain whether activation phenotypes and functional changes in T lymphocytes shape brain development. Here, we studied the effects of BCG vaccination via the adoptive transfer of T lymphocytes from the BALB/c wild-type mice into naive mice. Our results show that mice adoptive BCG-induced lymphocytes (BCG->naive mice) showed anxiolytic and antidepressant-like performance when completing an elevated plus maze (EPM) test. Meanwhile, BCG->naive mice possess more cell proliferation and newborn neurons than PBS->naive and nude mice in the hippocampus. IFN-γ and IL-4 levels in the serum of BCG->naive mice also increased, while TNF-α and IL-1β levels were reduced relative to those of PBS->naive and nude mice. We further found that BCG->naive mice showed different repartition of CD4+ and CD8+ T cell to naive (CD62L+ CD44low), effector memory (CD62L− CD44hi), central memory (CD62L+ CD44hi) and acute/activated effector (CD62L− CD44low) cells in the spleen. Importantly, the adoptive transfer of BCG-induced T lymphocytes infiltrated into the dura mater and brain parenchyma of the nude mice. Activation phenotypes and functional changes in T lymphocytes are very likely to affect the neuroimmune milieu in the brain, and alterations in ratios of splenic CD4+ and CD8+ memory T cells may affect the expression of correlative cytokines in the serum, accounting for our behavioral results. We conclude thus that the adoptive transfer of BCG-induced T lymphocytes contributes to hippocampal cell proliferation and tempers anxiety-like behavior in immune deficient mice. Our work shows that BCG vaccination improves hippocampal cell proliferation outcomes and behaviors, likely as a result of splenic effector/memory T lymphocytes regulating the neuroimmune niche in the brain.