Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies
| العنوان: | Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies |
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| المؤلفون: | Adam Denes, Nicolai Franzmeier, Steffanie Heindl, Olga Carofiglio, Thomas Arzberger, Peter T. Nelson, Nikolett Lénárt, Alessio Ricci, Tibor Hortobágyi, Arthur Liesz, Dieter Edbauer, Qihui Zhou, Ann M. Stowe |
| المصدر: | Journal of Experimental Medicine Journal of experimental medicine 218(8), e20202411 (2021). doi:10.1084/jem.20202411 The Journal of Experimental Medicine |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, immunology [Brain Ischemia], Male, therapy [Stroke], Lymphocyte, Integrin alpha4, T-Lymphocytes, Autopsy, Brain Ischemia, immunology [T-Lymphocytes], 0302 clinical medicine, Neuroinflammation, pathology [Brain], drug effects [Neuronal Plasticity], Immunology and Allergy, immunology [Integrin alpha4], Stroke, Neuronal Plasticity, physiopathology [Stroke], biology, Natalizumab, Brain, Pathophysiology, 3. Good health, medicine.anatomical_structure, drug therapy [Brain Ischemia], immunology [Brain], Female, Immunotherapy, Antibody, drug effects [Recovery of Function], T cell, Immunology, pharmacology [Natalizumab], therapeutic use [Natalizumab], pathology [Brain Ischemia], 03 medical and health sciences, medicine, Animals, Humans, cardiovascular diseases, ddc:610, Lymphocyte Count, Cell Proliferation, business.industry, Brief Definitive Report, Recovery of Function, medicine.disease, Clinical trial, Mice, Inbred C57BL, 030104 developmental biology, biology.protein, business, 030217 neurology & neurosurgery, immunology [Stroke], Neuroscience |
| الوصف: | Heindl et al. describe the local proliferation and clustering of T cells in the brain of mice and humans after stroke. This previously unrecognized phenomenon could explain why blocking cerebral leukocyte invasion might fail to improve long-term stroke recovery. 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. Graphical Abstract |
| تدمد: | 0022-1007 |
| DOI: | 10.1084/jem.20202411 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f85b3077423c61350254debe6602a6adTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f85b3077423c61350254debe6602a6ad |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00221007 |
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| DOI: | 10.1084/jem.20202411 |