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001     157717
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024 7 _ |a 10.1084/jem.20202411
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024 7 _ |a pmc:PMC8160576
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024 7 _ |a 1540-9358
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024 7 _ |a 1540-9538
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037 _ _ |a DZNE-2021-01174
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Heindl, Steffanie
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245 _ _ |a Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies.
260 _ _ |a New York, NY
|c 2021
|b Rockefeller Univ. Press
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a Neuroinflammation is an emerging focus of translational stroke research. Preclinical studies have demonstrated a critical role for brain-invading lymphocytes in post-stroke pathophysiology. Reducing cerebral lymphocyte invasion by anti-CD49d antibodies consistently improves outcome in the acute phase after experimental stroke models. However, clinical trials testing this approach failed to show efficacy in stroke patients for the chronic outcome 3 mo after stroke. Here, we identify a potential mechanistic reason for this phenomenon by detecting chronic T cell accumulation-evading the systemic therapy-in the post-ischemic brain. We observed a persistent accumulation of T cells in mice and human autopsy samples for more than 1 mo after stroke. Cerebral T cell accumulation in the post-ischemic brain was driven by increased local T cell proliferation rather than by T cell invasion. This observation urges re-evaluation of current immunotherapeutic approaches, which target circulating lymphocytes for promoting recovery after stroke.
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650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Autopsy
|2 MeSH
650 _ 2 |a Brain: immunology
|2 MeSH
650 _ 2 |a Brain: pathology
|2 MeSH
650 _ 2 |a Brain Ischemia: drug therapy
|2 MeSH
650 _ 2 |a Brain Ischemia: immunology
|2 MeSH
650 _ 2 |a Brain Ischemia: pathology
|2 MeSH
650 _ 2 |a Cell Proliferation
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Immunotherapy
|2 MeSH
650 _ 2 |a Integrin alpha4: immunology
|2 MeSH
650 _ 2 |a Lymphocyte Count
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Natalizumab: pharmacology
|2 MeSH
650 _ 2 |a Natalizumab: therapeutic use
|2 MeSH
650 _ 2 |a Neuronal Plasticity: drug effects
|2 MeSH
650 _ 2 |a Recovery of Function: drug effects
|2 MeSH
650 _ 2 |a Stroke: immunology
|2 MeSH
650 _ 2 |a Stroke: physiopathology
|2 MeSH
650 _ 2 |a Stroke: therapy
|2 MeSH
650 _ 2 |a T-Lymphocytes: immunology
|2 MeSH
700 1 _ |a Ricci, Alessio
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700 1 _ |a Carofiglio, Olga
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700 1 _ |a Zhou, Qihui
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700 1 _ |a Arzberger, Thomas
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700 1 _ |a Lenart, Nikolett
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700 1 _ |a Franzmeier, Nicolai
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700 1 _ |a Hortobagyi, Tibor
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700 1 _ |a Nelson, Peter T
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700 1 _ |a Stowe, Ann M
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700 1 _ |a Denes, Adam
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700 1 _ |a Edbauer, Dieter
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700 1 _ |a Liesz, Arthur
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773 _ _ |a 10.1084/jem.20202411
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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