Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies
| Autor: | 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 |
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| Rok vydání: | 2021 |
| Předmět: |
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 |
| Zdroj: | Journal of Experimental Medicine Journal of experimental medicine 218(8), e20202411 (2021). doi:10.1084/jem.20202411 The Journal of Experimental Medicine |
| ISSN: | 0022-1007 |
| DOI: | 10.1084/jem.20202411 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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