IL-2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells
IL-2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells
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IL-2mAb 通过抑制 CD8 T 细胞减少局灶性脑缺血后的脱髓鞘
DOI：
10.1111/cns.13084
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发表时间：
2019-04-01
影响因子：
5.5
通讯作者：
Wen，Da-Xiang
中科院分区：
文献类型：
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作者：
Zhou，Yu-Xi;Wang，Xin;Wen，Da-Xiang
脱髓鞘是白色物质损伤的主要病理改变之一，与T细胞介导的免疫反应密切相关。因此，我们调查的作用，IL-2单克隆抗体（IL-2 mAb，JES 6 - 1）在打击脱髓鞘在中风的晚期phase of stroke.MethodsIL-2 mAb或IgG同种型抗体（0.25 mg/kg），在大脑中动脉闭塞（MCAO）手术后2和48小时，腹腔注射。通过2，3，5-三苯氯化三唑染色、免疫荧光染色、流式细胞术和蛋白质印迹法测量脑体积、外周免疫细胞浸润、小胶质细胞活化和髓鞘丢失。腹膜内注射CD 8中和抗体（15 mg/kg）前1天MCAO手术，以确定CD 8 +T细胞对脱髓鞘lesions.ResultsIL-2 mAb治疗的作用减少脑梗死体积，衰减脱髓鞘，并改善长期感觉运动功能dMCAO后28天。在IL-2 mAb处理的小鼠中，CD 8 + T细胞的脑浸润和CD 8 +T细胞的外周活化均减弱。结论IL-2 mAb可保护脑缺血损伤后白色物质的完整性，改善脑缺血损伤后的长期感觉运动功能。CD 8 +T细胞的活化和脑浸润对卒中后脱髓鞘是有害的，可能是IL-2 mAb后处理保护卒中后白色物质完整性的主要靶点。
AimsDemyelination, one of the major pathological changes of white matter injury, is closely related to T‐cell–mediated immune responses. Thus, we investigate the role of an IL‐2 monoclonal antibody (IL‐2mAb, JES6‐1) in combatting demyelination during the late phase of stroke.MethodsIL‐2mAb or IgG isotype antibody (0.25 mg/kg) was injected intraperitoneally 2 and 48 hours after middle cerebral artery occlusion (MCAO) surgery. Infarct volume, peripheral immune cell infiltration, microglia activation, and myelin loss were measured by 2,3,5‐triphenyte trazoliumchloride staining, immunofluorescence staining, flow cytometry, and Western blot. Intraperitoneal CD8 neutralizing antibody (15 mg/kg) was injected 1 day before MCAO surgery to determine the role of CD8+T cells on demyelinating lesions.ResultsIL‐2mAb treatment reduced brain infarct volume, attenuated demyelination, and improved long‐term sensorimotor functions up to 28 days after dMCAO. Brain infiltration of CD8+T cells and peripheral activation of CD8+T cells were both attenuated in IL‐2 mAb‐treated mice. The protection of IL‐2mAb on demyelination was abolished in mice depleted of CD8+T cell 1 week after stroke.ConclusionsIL‐2mAb preserved white matter integrity and improved long‐term sensorimotor functions following cerebral ischemic injury. The activation and brain infiltration of CD8+T cells are detrimental for demyelination after stroke and may be the major target of IL‐2mAb posttreatment in the protection of white matter integrity after stroke.