Therapy with recombinant T-cell receptor ligand reduces infarct size and infiltrating inflammatory cells in brain after middle cerebral artery occlusion in mice.
Therapy with recombinant T-cell receptor ligand reduces infarct size and infiltrating inflammatory cells in brain after middle cerebral artery occlusion in mice.
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DOI：
10.1007/s11011-011-9241-2
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发表时间：
2011-06
影响因子：
3.6
通讯作者：
Offner, Halina A.
中科院分区：
文献类型：
--
作者：
Dziennis, Suzan;Mader, Sarah;Akiyoshi, Kozaburo;Ren, Xuefang;Ayala, Patricia;Burrows, Gregory G.;Vandenbark, Arthur A.;Herson, Paco S.;Hurn, Patricia D.;Offner, Halina A.
中风诱导外周免疫应答的双相效应，其涉及外周白细胞的早期激活，随后是严重的免疫抑制和脾脏萎缩。外周免疫细胞，包括T淋巴细胞，迁移到大脑并加剧发展中的梗死。重组T细胞受体（TCR）配体（RTL）551被设计为髓磷脂少突胶质细胞糖蛋白（MOG）反应性T细胞的部分TCR激动剂，并且已经证明当施用给经历大脑中动脉闭塞（MCAO）的小鼠时限制脑中的梗塞体积和炎症的能力。本研究的目的是确定当在目前临床实践中用于中风患者的治疗相关的4小时时间窗内给予时，RTL 551是否可以保持保护。在MCAO后4小时皮下施用RTL 551，每24小时重复给药直至安乐死的时间。在再灌注24和96小时后，评估脑、血液、脾和淋巴结中的细胞数量，并测量梗死面积。RTL551在MCAO后24小时和96小时减少皮质和纹状体中的梗死面积，并在两个时间点抑制脑中炎性细胞的积累。在MCAO后24小时，RTL 551降低了血液和缺血半球中T细胞上活化标志物CD44的频率。此外，RTL 551减少了趋化因子受体、淋巴结和脾脏中的CCR 5以及血液和淋巴结中的CCR 7的表达。这些数据证明了在治疗相关的4小时时间窗内通过髓鞘反应性炎性T细胞的免疫调节用RTL 551有效治疗实验性中风。
Stroke induces a biphasic effect on the peripheral immune response that involves early activation of peripheral leukocytes followed by severe immunosuppression and atrophy of the spleen. Peripheral immune cells, including T lymphocytes, migrate to the brain and exacerbate the developing infarct. Recombinant T-cell receptor (TCR) Ligand (RTL)551 is designed as a partial TCR agonist for myelin oligodendrocyte glycoprotein (MOG)-reactive T cells and has demonstrated the capacity to limit infarct volume and inflammation in brain when administered to mice undergoing middle cerebral artery occlusion (MCAO). The goal of this study was to determine if RTL551 could retain protection when given within the therapeutically relevant 4h time window currently in clinical practice for stroke patients. RTL551 was administered subcutaneously 4h after MCAO, with repeated doses every 24h until the time of euthanasia. Cell numbers were assessed in the brain, blood, spleen and lymph nodes and infarct size was measured after 24 and 96h reperfusion. RTL551 reduced infarct size in both cortex and striatum at 24h and in cortex at 96h after MCAO and inhibited the accumulation of inflammatory cells in brain at both time points. At 24h post-MCAO, RTL551 reduced the frequency of the activation marker, CD44, on T-cells in blood and in the ischemic hemisphere. Moreover, RTL551 reduced expression of the chemokine receptors, CCR5 in lymph nodes and spleen, and CCR7 in the blood and lymph nodes. These data demonstrate effective treatment of experimental stroke with RTL551 within a therapeutically relevant 4h time window through immune regulation of myelin-reactive inflammatory T-cells.
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影响因子：
5.3
作者：
Sinha, Sushmita;Subramanian, Sandhya;Offner, Halina
通讯作者：
Offner, Halina
影响因子：
3.6
作者：
Ebert, LA;Schaerli, P;Moser, B
通讯作者：
Moser, B
影响因子：
8.3
作者：
Gelderblom, Mathias;Leypoldt, Frank;Magnus, Tim
通讯作者：
Magnus, Tim
影响因子：
4.4
作者：
Burrows, GG;Adlard, KL;Offner, H
通讯作者：
Offner, H
DOI：
10.1084/jem.20021098
发表时间：
2003-09-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Prass K;Meisel C;Höflich C;Braun J;Halle E;Wolf T;Ruscher K;Victorov IV;Priller J;Dirnagl U;Volk HD;Meisel A
通讯作者：
Meisel A