Regulatory CD8(+)CD122 (+) T-cells predominate in CNS after treatment of experimental stroke in male mice with IL-10-secreting B-cells.
Regulatory CD8(+)CD122 (+) T-cells predominate in CNS after treatment of experimental stroke in male mice with IL-10-secreting B-cells.
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调节性CD8（+）CD122（+）T细胞在用IL-10分泌B细胞的雄性小鼠治疗实验性中风后CNS中占主导地位。
DOI：
10.1007/s11011-014-9639-8
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发表时间：
2015-08
影响因子：
3.6
通讯作者：
Offner H
中科院分区：
文献类型：
--
作者：
Bodhankar S;Chen Y;Lapato A;Vandenbark AA;Murphy SJ;Saugstad JA;Offner H
临床中风会诱发炎症过程，导致脑和脾损伤以及严重的外周免疫抑制。 IL-10 表达在主要中枢神经系统疾病期间升高，并限制大脑炎症。最近的证据表明，在大脑中动脉闭塞 (MCAO) 之前 24 小时或之后 4 小时，IL-10+ B 细胞的转移可减少雄性 C57BL/6J（野生型，WT）受体小鼠的梗塞体积。本研究的目的是确定在 MCAO 诱导后 24 小时注射到 B 细胞充足的雄性 WT 小鼠中时，被动转移的 IL-10+ B 细胞是否可以发挥治疗和免疫调节作用。结果表明，在 60 分钟闭塞和 96 小时再灌注后，与媒介物处理的对照小鼠相比，IL-10+ B 细胞处理的小鼠显着减少了同侧皮层和半球的梗死体积，并改善了神经功能缺损。与媒介物治疗的对照小鼠相比，MCAO保护的B细胞受体小鼠的脾萎缩较少，活化的炎症T细胞数量减少，T细胞浸润减少，缺血半球的炎症环境较少。这些免疫调节变化与脾脏和受 MCAO 影响的脑半球中分泌 IL-10 的 CD8+CD122+ Treg 细胞的主要出现一致。这项研究首次证明了 IL-10+ B 细胞在远超过 4 小时 tPA 治疗窗口的时间点治疗雄性 WT 小鼠 MCAO 中的主要神经保护作用，导致产生与脾脏保存和减少 CNS 炎症相关的占主导地位的 IL-10+CD8+CD122+ Treg 群体。
Clinical stroke induces inflammatory processes leading to cerebral and splenic injury and profound peripheral immunosuppression. IL-10 expression is elevated during major CNS diseases and limits inflammation in the brain. Recent evidence demonstrated that transfer of IL-10+ B-cells reduced infarct volume in male C57BL/6J (wild-type, WT) recipient mice when given 24 h prior to or 4 h after middle cerebral artery occlusion (MCAO). The purpose of this study was to determine if passively transferred IL-10+ B-cells can exert therapeutic and immunoregulatory effects when injected 24 hours after MCAO induction in B-cell-sufficient male WT mice. The results demonstrated that IL-10+ B-cell treated mice had significantly reduced infarct volumes in the ipsilateral cortex and hemisphere and improved neurological deficits vs. Vehicle-treated control mice after 60 min occlusion and 96 h of reperfusion. The MCAO-protected B-cell recipient mice had less splenic atrophy and reduced numbers of activated, inflammatory T-cells, decreased infiltration of T-cells and a less inflammatory milieu in the ischemic hemispheres compared with Vehicle-treated control mice. These immunoregulatory changes occurred in concert with the predominant appearance of IL-10-secreting CD8+CD122+ Treg cells in both the spleen and the MCAO-affected brain hemisphere. This study for the first time demonstrates a major neuroprotective role for IL-10+ B-cells in treating MCAO in male WT mice at a time point well beyond the ~4 h tPA treatment window, leading to the generation of a dominant IL-10+CD8+CD122+ Treg population associated with spleen preservation and reduced CNS inflammation.