T-lymphocytes have a multifaceted role in ischemic stroke, but the majority of studies have been conducted in young mice, which may limit the translational value of these findings. Previous studies have shown that aging results in T cell dysfunction, leading to enhanced production of pro-inflammatory cytokines and chemokines, including interferon gamma (IFN-γ) and interferon-gamma-inducible protein (IP-10). This study assessed the role of T cells and pro-inflammatory factors on histologic and functional outcomes in an aged mouse model. Levels of IP-10 were measured in the brain and serum of young and aged male mice following middle cerebral artery occlusion (MCAo) or sham surgery. Additionally, IP-10 levels were evaluated in stroke patients. To directly determine the role of brain-infiltrating T cells after stroke, a separate cohort of aged male and female animals received either an anti-CD4 depletion antibody or IgG isotype control at 72 and 96 h following experimental stroke. Behavioral assessments were performed on day 7 post-MCAo. CD4 T cell depletion resulted in improved behavioral outcomes, despite the lack of differences in infarct size between the isotype control and anti-CD4 antibody treated stroke groups. Circulating IP-10 levels were increased in both humans and mice with age and stroke, and depletion of CD4 T cells led to a reduction in IFN-γ and IP-10 levels in mice. Since anti-CD4 treatment was administered three days after stroke onset, targeting this inflammatory pathway may be beneficial to aged stroke patients who present outside of the current time window for thrombolysis and thrombectomy.

中文翻译：

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CD4 T 细胞的消耗为缺血性中风后的老年小鼠提供了治疗益处。

T 淋巴细胞在缺血性中风中具有多方面的作用，但大多数研究都是在年轻小鼠中进行的，这可能会限制这些发现的转化价值。先前的研究表明，衰老会导致 T 细胞功能障碍，导致促炎细胞因子和趋化因子的产生增加，包括干扰素 γ (IFN-γ) 和干扰素γ 诱导蛋白 (IP-10)。本研究评估了 T 细胞和促炎因子对老年小鼠模型的组织学和功能结果的作用。在大脑中动脉闭塞 (MCAo) 或假手术后，在年轻和老年雄性小鼠的大脑和血清中测量 IP-10 的水平。此外，还评估了中风患者的 IP-10 水平。为了直接确定中风后脑浸润 T 细胞的作用，一组单独的老年雄性和雌性动物在实验性中风后 72 和 96 小时接受了抗 CD4 耗竭抗体或 IgG 同种型对照。在 MCAo 后第 7 天进行行为评估。尽管同种型对照和抗 CD4 抗体治疗的卒中组之间的梗死面积没有差异，但 CD4 T 细胞耗竭导致行为结果的改善。人类和中风小鼠的循环 IP-10 水平增加，CD4 T 细胞的消耗导致小鼠 IFN-γ 和 IP-10 水平的降低。由于抗 CD4 治疗是在中风发作后三天进行的，针对这一炎症途径可能对在当前时间窗外进行溶栓和血栓切除术的老年中风患者有益。