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IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells
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| Zeitschriftentitel: | CNS Neuroscience & Therapeutics |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , , |
| In: | CNS Neuroscience & Therapeutics, 25, 2019, 4, S. 532-543 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
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| Schlagwörter: |
| author_facet |
Zhou, Yu‐Xi Wang, Xin Tang, Dan Li, Yan Jiao, Ying‐Fu Gan, Yu Hu, Xiao‐Ming Yang, Li‐Qun Yu, Wei‐Feng Stetler, Ruth Anne Li, Pei‐Ying Wen, Da‐Xiang Zhou, Yu‐Xi Wang, Xin Tang, Dan Li, Yan Jiao, Ying‐Fu Gan, Yu Hu, Xiao‐Ming Yang, Li‐Qun Yu, Wei‐Feng Stetler, Ruth Anne Li, Pei‐Ying Wen, Da‐Xiang |
|---|---|
| author |
Zhou, Yu‐Xi Wang, Xin Tang, Dan Li, Yan Jiao, Ying‐Fu Gan, Yu Hu, Xiao‐Ming Yang, Li‐Qun Yu, Wei‐Feng Stetler, Ruth Anne Li, Pei‐Ying Wen, Da‐Xiang |
| spellingShingle |
Zhou, Yu‐Xi Wang, Xin Tang, Dan Li, Yan Jiao, Ying‐Fu Gan, Yu Hu, Xiao‐Ming Yang, Li‐Qun Yu, Wei‐Feng Stetler, Ruth Anne Li, Pei‐Ying Wen, Da‐Xiang CNS Neuroscience & Therapeutics IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells Pharmacology (medical) Physiology (medical) Psychiatry and Mental health Pharmacology |
| author_sort |
zhou, yu‐xi |
| spelling |
Zhou, Yu‐Xi Wang, Xin Tang, Dan Li, Yan Jiao, Ying‐Fu Gan, Yu Hu, Xiao‐Ming Yang, Li‐Qun Yu, Wei‐Feng Stetler, Ruth Anne Li, Pei‐Ying Wen, Da‐Xiang 1755-5930 1755-5949 Wiley Pharmacology (medical) Physiology (medical) Psychiatry and Mental health Pharmacology http://dx.doi.org/10.1111/cns.13084 <jats:title>Summary</jats:title><jats:sec><jats:title>Aims</jats:title><jats:p>Demyelination, 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>IL‐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<jats:sup>+</jats:sup> T cells on demyelinating lesions.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>IL‐2mAb treatment reduced brain infarct volume, attenuated demyelination, and improved long‐term sensorimotor functions up to 28 days after dMCAO. Brain infiltration of CD8<jats:sup>+</jats:sup> T cells and peripheral activation of CD8<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> T cell 1 week after stroke.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>IL‐2mAb preserved white matter integrity and improved long‐term sensorimotor functions following cerebral ischemic injury. The activation and brain infiltration of CD8<jats:sup>+</jats:sup> 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.</jats:p></jats:sec> IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8<sup>+</sup> T cells CNS Neuroscience & Therapeutics |
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10.1111/cns.13084 |
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Online Free |
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Wiley, 2019 |
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Wiley, 2019 |
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1755-5930 1755-5949 |
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CNS Neuroscience & Therapeutics |
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| title |
IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells |
| title_unstemmed |
IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells |
| title_full |
IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells |
| title_fullStr |
IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells |
| title_full_unstemmed |
IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells |
| title_short |
IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells |
| title_sort |
il‐2mab reduces demyelination after focal cerebral ischemia by suppressing cd8<sup>+</sup> t cells |
| topic |
Pharmacology (medical) Physiology (medical) Psychiatry and Mental health Pharmacology |
| url |
http://dx.doi.org/10.1111/cns.13084 |
| publishDate |
2019 |
| physical |
532-543 |
| description |
<jats:title>Summary</jats:title><jats:sec><jats:title>Aims</jats:title><jats:p>Demyelination, 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>IL‐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<jats:sup>+</jats:sup> T cells on demyelinating lesions.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>IL‐2mAb treatment reduced brain infarct volume, attenuated demyelination, and improved long‐term sensorimotor functions up to 28 days after dMCAO. Brain infiltration of CD8<jats:sup>+</jats:sup> T cells and peripheral activation of CD8<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> T cell 1 week after stroke.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>IL‐2mAb preserved white matter integrity and improved long‐term sensorimotor functions following cerebral ischemic injury. The activation and brain infiltration of CD8<jats:sup>+</jats:sup> 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.</jats:p></jats:sec> |
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| author | Zhou, Yu‐Xi, Wang, Xin, Tang, Dan, Li, Yan, Jiao, Ying‐Fu, Gan, Yu, Hu, Xiao‐Ming, Yang, Li‐Qun, Yu, Wei‐Feng, Stetler, Ruth Anne, Li, Pei‐Ying, Wen, Da‐Xiang |
| author_facet | Zhou, Yu‐Xi, Wang, Xin, Tang, Dan, Li, Yan, Jiao, Ying‐Fu, Gan, Yu, Hu, Xiao‐Ming, Yang, Li‐Qun, Yu, Wei‐Feng, Stetler, Ruth Anne, Li, Pei‐Ying, Wen, Da‐Xiang, Zhou, Yu‐Xi, Wang, Xin, Tang, Dan, Li, Yan, Jiao, Ying‐Fu, Gan, Yu, Hu, Xiao‐Ming, Yang, Li‐Qun, Yu, Wei‐Feng, Stetler, Ruth Anne, Li, Pei‐Ying, Wen, Da‐Xiang |
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| description | <jats:title>Summary</jats:title><jats:sec><jats:title>Aims</jats:title><jats:p>Demyelination, 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>IL‐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<jats:sup>+</jats:sup> T cells on demyelinating lesions.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>IL‐2mAb treatment reduced brain infarct volume, attenuated demyelination, and improved long‐term sensorimotor functions up to 28 days after dMCAO. Brain infiltration of CD8<jats:sup>+</jats:sup> T cells and peripheral activation of CD8<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> T cell 1 week after stroke.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>IL‐2mAb preserved white matter integrity and improved long‐term sensorimotor functions following cerebral ischemic injury. The activation and brain infiltration of CD8<jats:sup>+</jats:sup> 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.</jats:p></jats:sec> |
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| imprint | Wiley, 2019 |
| imprint_str_mv | Wiley, 2019 |
| institution | DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229 |
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| spelling | Zhou, Yu‐Xi Wang, Xin Tang, Dan Li, Yan Jiao, Ying‐Fu Gan, Yu Hu, Xiao‐Ming Yang, Li‐Qun Yu, Wei‐Feng Stetler, Ruth Anne Li, Pei‐Ying Wen, Da‐Xiang 1755-5930 1755-5949 Wiley Pharmacology (medical) Physiology (medical) Psychiatry and Mental health Pharmacology http://dx.doi.org/10.1111/cns.13084 <jats:title>Summary</jats:title><jats:sec><jats:title>Aims</jats:title><jats:p>Demyelination, 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.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>IL‐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<jats:sup>+</jats:sup> T cells on demyelinating lesions.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>IL‐2mAb treatment reduced brain infarct volume, attenuated demyelination, and improved long‐term sensorimotor functions up to 28 days after dMCAO. Brain infiltration of CD8<jats:sup>+</jats:sup> T cells and peripheral activation of CD8<jats:sup>+</jats:sup> 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<jats:sup>+</jats:sup> T cell 1 week after stroke.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>IL‐2mAb preserved white matter integrity and improved long‐term sensorimotor functions following cerebral ischemic injury. The activation and brain infiltration of CD8<jats:sup>+</jats:sup> 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.</jats:p></jats:sec> IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8<sup>+</sup> T cells CNS Neuroscience & Therapeutics |
| spellingShingle | Zhou, Yu‐Xi, Wang, Xin, Tang, Dan, Li, Yan, Jiao, Ying‐Fu, Gan, Yu, Hu, Xiao‐Ming, Yang, Li‐Qun, Yu, Wei‐Feng, Stetler, Ruth Anne, Li, Pei‐Ying, Wen, Da‐Xiang, CNS Neuroscience & Therapeutics, IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells, Pharmacology (medical), Physiology (medical), Psychiatry and Mental health, Pharmacology |
| title | IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells |
| title_full | IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells |
| title_fullStr | IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells |
| title_full_unstemmed | IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells |
| title_short | IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells |
| title_sort | il‐2mab reduces demyelination after focal cerebral ischemia by suppressing cd8<sup>+</sup> t cells |
| title_unstemmed | IL‐2mAb reduces demyelination after focal cerebral ischemia by suppressing CD8+ T cells |
| topic | Pharmacology (medical), Physiology (medical), Psychiatry and Mental health, Pharmacology |
| url | http://dx.doi.org/10.1111/cns.13084 |